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PurposeTo elucidate the molecular events in solute carrier family 4 member 11 (SLC4A11)-deficient corneal endothelium that lead to the endothelial dysfunction that characterizes the dystrophies associated with SLC4A11 mutations, congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy 4.MethodsComparative transcriptomic analysis (CTA) was performed in primary human corneal endothelial cells (pHCEnC) and murine corneal endothelial cells (MCEnC) with normal and reduced levels of SLC4A11 (SLC4A11 KD pHCEnC) and Slc4a11 (Slc4a11-/- MCEnC), respectively. Validation of differentially expressed genes was performed using immunofluorescence staining of CHED corneal endothelium, as well as western blot and quantitative PCR analysis of SLC4A11 KD pHCEnC and Slc4a11-/- MCEnC. Functional analyses were performed to investigate potential functional changes associated with the observed transcriptomic alterations.ResultsCTA revealed inhibition of cell metabolism and ion transport function as well as mitochondrial dysfunction, leading to reduced adenosine triphosphate (ATP) production, in SLC4A11 KD pHCEnC and Slc4a11-/- MCEnC. Co-localization of SNARE protein STX17 with mitochondria marker COX4 was observed in CHED corneal endothelium, as was activation of AMPK-p53/ULK1 in both SLC4A11 KD pHCEnC and Slc4a11-/- MCEnC, providing additional evidence of mitochondrial dysfunction and mitophagy. Reduced Na+-dependent HCO3- transport activity and altered NH4Cl-induced membrane potential changes were observed in Slc4a11-/- MCEnC.ConclusionsReduced steady-state ATP levels and subsequent activation of the AMPK-p53 pathway provide a link between the metabolic functional deficit and transcriptome alterations, as well as evidence of insufficient ATP to maintain the Na+/K+-ATPase corneal endothelial pump as the cause of the edema that characterizes SLC4A11-associated corneal endothelial dystrophies.

Synaptic vesicles accumulate neurotransmitters, enabling the quantal release by exocytosis that underlies synaptic transmission. Specific neurotransmitter transporters are responsible for this activity and therefore are essential for brain function. The vesicular glutamate transporters (VGLUTs) concentrate the principal excitatory neurotransmitter glutamate into synaptic vesicles, driven by membrane potential. However, the mechanism by which they do so remains poorly understood owing to a lack of structural information. We report the cryo-electron microscopy structure of rat VGLUT2 at 3.8-angstrom resolution and propose structure-based mechanisms for substrate recognition and allosteric activation by low pH and chloride. A potential permeation pathway for chloride intersects with the glutamate binding site. These results demonstrate how the activity of VGLUTs can be coordinated with large shifts in proton and chloride concentrations during the synaptic vesicle cycle to ensure normal synaptic transmission.

Cation-chloride-cotransporters (CCCs) catalyze transport of Cl- with K+ and/or Na+across cellular membranes. CCCs play roles in cellular volume regulation, neural development and function, audition, regulation of blood pressure, and renal function. CCCs are targets of clinically important drugs including loop diuretics and their disruption has been implicated in pathophysiology including epilepsy, hearing loss, and the genetic disorders Andermann, Gitelman, and Bartter syndromes. Here we present the structure of a CCC, the Mus musculus K+-Cl- cotransporter (KCC) KCC4, in lipid nanodiscs determined by cryo-EM. The structure, captured in an inside-open conformation, reveals the architecture of KCCs including an extracellular domain poised to regulate transport activity through an outer gate. We identify binding sites for substrate K+ and Cl- ions, demonstrate the importance of key coordinating residues for transporter activity, and provide a structural explanation for varied substrate specificity and ion transport ratio among CCCs. These results provide mechanistic insight into the function and regulation of a physiologically important transporter family.

Mixtures of neutral polymers and lithium salts have the potential to serve as electrolytes in next-generation rechargeable Li-ion batteries. The purpose of this review is to expose the delicate interplay between polymer-salt interactions at the segmental level and macroscopic ion transport at the battery level. Since complete characterization of this interplay has only been completed in one system: mixtures of poly(ethylene oxide) and lithium bis(trifluoromethanesulfonyl)imide (PEO/LiTFSI), we focus on data obtained from this system. We begin with a discussion of the activity coefficient, followed by a discussion of six different diffusion coefficients: the Rouse motion of polymer segments is quantified by Dseg, the self-diffusion of cations and anions is quantified by Dself,+ and Dself,−, and the build-up of concentration gradients in electrolytes under an applied potential is quantified by Stefan-Maxwell diffusion coefficients, D0+, D0-, and D+-. The Stefan-Maxwell diffusion coefficients can be used to predict the velocities of the ions at very early times after an electric field is applied across the electrolyte. The surprising result is that D0- is negative in certain concentration windows. A consequence of this finding is that at these concentrations, both cations and anions are predicted to migrate toward the positive electrode at early times. We describe the controversies that surround this result. Knowledge of the Stefan-Maxwell diffusion coefficients enable prediction of the limiting current. We argue that the limiting current is the most important characteristic of an electrolyte. Excellent agreement between theoretical and experimental limiting current is seen in PEO/LiTFSI mixtures. What sequence of monomers that, when polymerized, will lead to the highest limiting current remains an important unanswered question. It is our hope that the approach presented in this review will guide the development of such polymers.

Mixtures of neutral polymers and lithium salts have the potential to serve as electrolytes in next-generation rechargeable Li-ion batteries. The purpose of this review is to expose the delicate interplay between polymer-salt interactions at the segmental level and macroscopic ion transport at the battery level. Since complete characterization of this interplay has only been completed in one system: mixtures of poly(ethylene oxide) and lithium bis(trifluoromethanesulfonyl)imide (PEO/LiTFSI), we focus on data obtained from this system. We begin with a discussion of the activity coefficient, followed by a discussion of six different diffusion coefficients: the Rouse motion of polymer segments is quantified by Dseg, the self-diffusion of cations and anions is quantified by Dself,+ and Dself,−, and the build-up of concentration gradients in electrolytes under an applied potential is quantified by Stefan-Maxwell diffusion coefficients, D0+, D0-, and D+-. The Stefan-Maxwell diffusion coefficients can be used to predict the velocities of the ions at very early times after an electric field is applied across the electrolyte. The surprising result is that D0- is negative in certain concentration windows. A consequence of this finding is that at these concentrations, both cations and anions are predicted to migrate toward the positive electrode at early times. We describe the controversies that surround this result. Knowledge of the Stefan-Maxwell diffusion coefficients enable prediction of the limiting current. We argue that the limiting current is the most important characteristic of an electrolyte. Excellent agreement between theoretical and experimental limiting current is seen in PEO/LiTFSI mixtures. What sequence of monomers that, when polymerized, will lead to the highest limiting current remains an important unanswered question. It is our hope that the approach presented in this review will guide the development of such polymers.

Cadmium (Cd) toxicity affects many crops. Members of the OsNramp (Natural resistance-associated macrophage protein) gene family play important roles in the transport of divalent or trivalent cations in rice (Oryza sativa L.). This study explored a possible involvement of OsNramp4 in Cd2+ transport in rice. We employed the CRISPR/cas9 technique to obtain rice OsNramp4 knockout lines. Using NMT (Non-invasive Micro-test Technology) system for real-time measurement, it was found that the net Cd2+ flux was significantly lower than that of wild-type. The yeast strain expressing OsNramp4 grew poorly under Cd2+ stress, and accumulated more Cd2+ than the control strain, which enhanced the sensitivity of yeast to Cd2+. OsNramp4 was membrane-localized and mainly expressed in roots, but after tillering, its expression shifted to the nodes and glumes. Furthermore, the loss-of-function OsNramp4 mutation lowered the root cell sap Cd2+ content, resulting in a significant decrease in Cd2+ content in shoot and Cd2+ accumulation in grains. We characterized the OsNramp4, an Al3+ transporter with the ability to alter the cellular distribution of Cd2+ in rice and to reduce Cd2+ content in the grain. Our study highlights the complexity of ion uptake and transport in plants.

Lithium dendrite formation and insufficient ionic conductivity remain primary concerns for the utilization of solid‐state batteries. Given that the interpretation of experimental results for polycrystalline solid electrolytes can be difficult, computational techniques are invaluable for providing insight at the atomic scale. Here, first‐principles calculations are carried out on representative grain boundaries in four important solid electrolytes, namely, an anti‐perovskite oxide, Li3OCl, and its hydrated counterpart, Li2OHCl, a thiophosphate, Li3PS4, and a halide, Li3InCl6, to develop the first generally applicable design principles for grain boundaries in solid electrolytes for solid‐state batteries. The significantly different impacts that grain boundaries have on electronic structure and transport, ion conductivity and correlated ion dynamics are demonstrated. The results show that even when grain boundaries do not significantly impact ionic conductivity, they can still strongly perturb the electronic structure and contribute to potential lithium dendrite propagation. It is also illustrated, for the first time, how correlated motion, including the so‐called paddle‐wheel mechanism, can vary substantially at grain boundaries. These findings reveal the dramatically different behavior of solid electrolytes at the microscale compared to the bulk and its potential consequences and benefits for the design of solid‐state batteries. These design principles are expected to aid the synthesis and engineering of solid electrolytes at the microscale for preventing dendrite propagation and accelerating ion transport. [ABSTRACT FROM AUTHOR]

Dynamic changes in aquaporin gene expression occur during seed germination. One example is the ~30-fold increase in Arabidopsis thaliana PIP2;1 transcripts within 24 h of seed imbibition. To investigate whether AtPIP2;1 can influence seed germination wild-type Columbia-0, single (Atpip2;1) and double (Atpip2;1-Atpip2;2) loss-of-function mutants, along with transgenic 2x35S::AtPIP2;1 over-expressing (OE) lines and null-segregant controls, were examined. The various genotypes were germinated in control and saline (75 mM NaCl treatment) conditions and tested for germination efficiency, imbibed seed maximum cross sectional (MCS) area, imbibed seed mass, and seed Na+ and K+ content. Seed lacking functional AtPIP2;1 and/or AtPIP2;2 proteins or constitutively over-expressing AtPIP2;1 , had delayed germination in saline conditions relative to wild-type and null-segregant seed, respectively. Exposure to saline germination conditions resulted in Atpip2;1 mutants having greater imbibed seed mass and less accumulated Na+ than wild-type, whereas lines over-expressing AtPIP2;1 had reduced imbibed seed mass and greater seed K+ content than null-segregant control seed. The results imply a role for AtPIP2;1 in seed germination processes, whether directly through its capacity for water and ion transport or H2O2 signalling, or indirectly through potentially triggering dynamic differential regulation of other aquaporins expressed during germination. Future research will aid in dissecting the aquaporin functions influencing germination and may lead to novel solutions for optimising germination in sub-optimal conditions, such as saline soils. This study explored the role of Arabidopsis thaliana plasma membrane intrinsic protein (AtPIP2;1) in seed germination. Seed from plants varying in their relative abundance of AtPIP2;1 differed in the timing of germination in saline conditions relative to seed from wild-type plants. Wild-type seed germinated faster in saline conditions than the seed which had lost AtPIP2;1 function and the seed with a greater abundance of AtPIP2;1. [ABSTRACT FROM AUTHOR]

Soil salinity is a worldwide problem that adversely affects plant growth and development. Soil salinization in Xinjiang of China is very serious. Ping'ou hybrid hazelnut, as an important ecological and economic tree species, as well as a salt-tolerant plant, has been grown in Xinjiang for over 20 years. Understanding the salt-tolerance mechanism of Ping'ou hybrid hazelnut is of great significance for the breeding of salt-tolerant varieties and the rational utilization of salinized land. In this study, 'Liaozhen 7', a fine variety of Ping'ou hybrid hazelnut, was selected as test material, and seedlings were treated with 0 (control), 50, 100 and 200 mM NaCl. Subsequently, the pattern of NaCl-induced fluxes of Na+, K+ and H+ in the root meristematic zone and their response to ion transport inhibitors were studied using non-invasive micro-test technology (NMT). Different concentrations of NaCl stress significantly increased the Na+ concentration in roots, while K+ concentration decreased first and then increased with the increase of NaCl concentration. Meanwhile, NaCl stress induced a significant decline in K+/Na+ ratio. Control and 200 mM NaCl-induced Na+ and K+ fluxes in roots exhibited an outward efflux, whereas an inward flux was observed for H+. Under 200 mM NaCl stress, the average rates of net Na+ and K+ efflux, as well as H+ influx in roots were significantly increased, which were 11.6, 6.7 and 2.3 times higher than that of control, respectively. Furthermore, pharmacological experiments showed that 200 mM NaCl-induced Na+ efflux; H+ influx was significantly suppressed by amiloride, an inhibitor of plasma membrane (PM) Na+/H+ antiporter, and sodium vanadate, an inhibitor of PM H+-ATPase. Net Na+ efflux and H+ influx induced by NaCl decreased by 89.9% and 135.0%, respectively. The NaCl-induced Na+ efflux was mediated by a Na+/H+ antiporter using energy provided by PM H+-ATPase. The NaCl-induced K+ efflux was significantly restricted by tetraethylamine chloride, a K+ channel inhibitor, and promoted by sodium vanadate, which decreased by 111.2% and increased by 80.8%, respectively, indicating that K+ efflux was regulated by depolarization-activated outward-rectifying K+ channels and non-selective cation channels (NSCCs). In conclusion, NMT data revealed that NaCl stress up regulated the root Na+/H+ antiporter and H+ pump (an activity of PM Na+/H+ antiport system) of 'Liaozhen 7', which compelled the Na+/H+ exchange across the PM and restricted K+ loss via depolarization-activated K+ channels and NSCCs simultaneously, thereby maintaining the K+/Na+ homeostasis and higher salt tolerance. [ABSTRACT FROM AUTHOR]

Coupling low-grade heat (LGH) with salinity gradient is an effective approach to increase the efficiency of the nanofluidic-membrane-based power generator. However, it is a challenge to fabricate membranes with high charge density that ensures ion permselectivity, while maintaining chemical and mechanical stability in this composite environment. Here, we develop a bis[2-(methacryloyloxy)ethyl] phosphate (BMAP) hydrogel membrane with good thermal stability and anti-swelling property through self-crosslinking of the selected monomer. By taking advantage of negative space charge and three-dimensional (3D) interconnected nanochannels, salinity gradient energy conversion efficiency is substantially enhanced by temperature difference. Theoretical and experimental results verify that LGH can largely weaken the concentration polarization, promoting transmembrane ion transport. As a result, such a hydrogel membrane delivers high-performance energy conversion with a power density of 11.53 W·m−2 under a negative temperature difference (NTD), showing a 193% increase compared with that without NTD. [ABSTRACT FROM AUTHOR]

As a mass transport media, water is an alternative of organic solvent applied in rechargeable batteries, due to its unique properties, including fast ionic migration, easy-processibility, economic/environmental friendliness, and flame retardancy. However, due to the high activity of water molecules in aqueous electrolytes, the corrosion of metal anode, side reactions, and inferior metal electrodeposition behavior leads to unstable cycling performance, poor Coulombic efficiency (CE), and early-staged failure of batteries. Despite several attempts to regulate the activity of water, migration of ions is sacrificed, due to the limited methods to control the water states. Herein, we developed a subnanoscale confinement strategy based on a nacre-like structure to modulate the activity of water in the solid electrolytes. By tuning the ratio between the two-dimensional (2D) vermiculite and one-dimensional (1D) cellulose nanofibers (CNFs), the capillary size in the 1D/2D structure is altered to achieve a fast Zn2+ transport. Our dielectric relaxation and molecular dynamics studies indicate that the enhanced Zn2+ conductivity is attributed to the fast water relaxation in the precisely defined 1D/2D capillary. Taking advantage of the regulated activity of the confined water in 2D capillary, the composite vermiculite membrane can suppress the corrosion and side reactions between Zn electrode and water molecular, endowing a reversible Zn2+ stripping/plating behavior and a stable cycling performance for 900 h. Based on our confinement strategy to control the water states by 1D/2D structures, this work will open an avenue toward aqueous energy storage devices with excellent reversibility, high safety, and long-term stability. [ABSTRACT FROM AUTHOR]

The aim of this study is to utilize the electromembrane extraction (EME) system as a manner for effective removal of zinc from aqueous solutions. A novel and distinctive electrochemical cell design was adopted consisting of two glass chambers, a supported liquid membrane (SLM) housing a polypropylene flat membrane infused with 1-octanol and a carrier. Two electrodes were used, a graphite as anode and a stainless steel as cathode. A comprehensive examination of several influential factors including the choice of carrier, the applied voltage magnitude, the initial pH of the donor solution, and the initial concentration of zinc was performed, all in a concerted effort to ascertain their respective impacts on the efficiency of zinc elimination. Two distinct carriers, namely tris(2-ethylhexyl) phosphate (TEHP) and bis(2-ethylhexyl) phosphate (DEHP) were evaluated, in a tandem with utilization of 1-octanol. The results revealed essential role played by the applied voltage in augmenting the rate of mass transfer of zinc across the membrane. The best operating conditions were utilized for 1-octanol enriched with 1.0 vol.% bis(2-ethylhexyl) phosphate as a carrier, applied voltage of 60 V, initial pH of 5, initial zinc concentration of 15 mg L-1, extraction duration of 6 hours, and stirring rate of 1000 rpm. Surprisingly, operating under these meticulously devised conditions culminated in the outstanding removal efficiency of 87.3 %. In comparison with no applied voltage, a substantial enhancement in removal efficiency was observed, trans­cending from a meager 36.67 % to an impressive 87.3 % at 60 V, suggesting thus a tremen­dous potential of EME as an efficacious technique for the elimination of heavy metals.

Abstract Nanofluidic systems exhibit transport characteristics that have made technological marvels such as desalination and energy harvesting possible by virtue of their ability to influence small currents due to selective ion transport. Traditionally, these applications have relied on nanoporous membranes whose complicated geometry impedes a comprehensive understanding of the underlying physics. To bypass the associated difficulties, we consider the simpler nanochannel array and elucidate the effects of interchannel interactions on the Ohmic response. It is demonstrated that a nanochannel array is equivalent to an array of mutually independent but identical unit‐cells whereby the array can be represented by an equivalent electrical circuit of resistances connected in a parallel configuration. The model is validated using numerical simulations and experiments. The approach to modeling nanofluidic systems by their equivalent electrical circuit provides an invaluable tool for analyzing and interpreting experimental measurements.

Abstract This review covers the evolution of flexible mechanical sensors from an “electronic” language to an “ionic” language, which provides key reference information for the development of next‐generation bio‐intelligent sensing devices. Unlike sensors that rely solely on electron modulation, the core feature of the ionic flexible mechanical sensor (IFMS) is the ability of mechanical deformation to induce ion transport and compensation, thus demonstrating their conceptual similarity to biomechanical strain systems. Here, the basic design principles of flexible mechanical sensors modulated by ion transport are highlighted. This review provides a detailed description of the mechanotransduction mechanisms of IFMS devices based on ion transport modulation. First, although with similar mechanisms to conventional flexible mechanical sensors via piezoresistive, piezoelectric, and triboelectric transduction mechanisms, the core driver for IFMS devices is ions (not electrons). In addition, the transduction models and principles of action of novel transduction mechanisms that have been explored in the last decade are described in detail, which include interfacial iontronic sensing and potentiometric and electrokinetic energy conversion. According to the characteristics of the device, the relevant structural engineering is further highlighted. A comprehensive review of important IFMS application approaches (human–machine interfaces, life and health applications) is presented. Importantly, future challenges and possible solutions for IFMS devices are presented based on the existing research.

The osmotic photobioreactor (OsPBR) technology has shown great potential by integrating forward osmosis with algal wastewater treatment. However, the reverse salt flux remains a key challenge. In order to reveal the diffusion behaviors and the transport mechanisms of reverse salt flux (RSF) in an OsPBR, the NH 4 HCO 3 and (NH 4) 2 HPO 4 (DAP) were compared as draw solutions. The results showed that the biomass growth in OsPBR with NH 4 HCO 3 as draw solution was higher than that of DAP initially, reached up to 0.78 g L−1. Although the reverse salt flux of NH 4 HCO 3 was twice higher than that of DAP, the OsPBR using NH 4 HCO 3 as draw solution exhibited better N & P removal rate than that of DAP, reached at 75% and 100%, respectively. A higher diffusion of cation to anion was further found for DAP as draw solution. This work showed the feasibility to use NH 4 HCO 3 as draw solution in OsPBR, which allows the upgrade of microalgal osmotic photobioreactor technology not only in water treatment but also its carbon neutralization potential. [Display omitted] • An osmotic photobioreactor using NH 4 HCO 3 as draw solution was proposed. • The osmotic photobioreactor using NH 4 HCO 3 as draw solution exhibited better N & P removal rate than that of DAP. • The reverse salt flux of NH 4 HCO 3 increased by electrolytes can be mitigated by microalgae. • A higher diffusion of cation relative to anion was found for DAP as draw solution. • It upgraded both the bidirectional diffusion mechanisms and algal water treatment. [ABSTRACT FROM AUTHOR]

As a copper (Cu) transport ATPase, ATP7A plays an important role in maintaining Cu homeostasis in the body, but the developmental and physiological roles of atp7a in zebrafish embryogenesis are rarely studied. In this study, normal morphological phenotypes of atp7a-/- homozygous zebrafish were observed at both embryonic and adult stages, however, atp7a-/- larvae exhibited delayed touch response and obvious transcriptome changes. Compared with the WT (wild type), differentially expressed genes (DEGs) in atp7a-/- larvae showed the enrichment in gene ontology (GO) terms related to several processes including ATPase activity, oxidoreductase activity, active transmembrane transporter activity, ion binding, and the citrate cycle. Furthermore, decreases in both ATP content and Naþ/Kþ-ATPase activity in atp7a-/- embryos and larvae were unveiled. 57 overlapping DEGs were found both in WT stressed with Cu and in WT mutated with atp7a, and GO term analysis indicated the enrichment in the genes related to neurexin family protein binding and neuronal cell-cell adhesion. Moreover, 42 overlapping DEGs in Cu stressed WT and Cu stressed atp7a-/- were identified. GO term analysis showed an enrichment in the genes related to heme binding, implying that Cu was independent of the integral function of atp7a to affect heme binding. In addition, genes involved in the negative regulation of angiogenesis were down-regulated in atp7a-/- mutants with and without Cu stress, which failed to occur in WT, implying that the integral function of atp7a is required for maintaining the normal expression of angiogenesis genes. The integrative data in this study demonstrated that atp7a is required for ion transport and angiogenesis, and for Cu-induced neurexin family protein binding defects, rather than for Cu-induced heme binding defects, during zebrafish embryogenesis. These findings provide possible clues for human diseases with ATP7A dysfunction and imbalanced Cu homeostasis. [ABSTRACT FROM AUTHOR]

Metal–metal battery bears great potential for next‐generation large‐scale energy storage system because of its simple manufacture process and low production cost. However, the cross‐over of metal cations from the cathode to the anode causes a loss in capacity and influences battery stability. Herein, a coating of poly (ionic liquid) (PIL) with poly(diallyldimethylammonium bis(trifluoromethanesulfonyl)imide) (PDADMA+TFSI−) on a commercial polypropylene (PP) separator serves as an anion exchange membrane for a 3.3 V copper–lithium battery. The PIL has a positively charged polymer backbone that can block the migration of copper ions, thus improving Coulombic efficiency, long‐term cycling stability and inhibiting self‐discharge of the battery. It can also facilitate the conduction of anions through the membrane and reduce polarization, especially for fast charging/discharging. Bruce‐Vincent method gives the transport number in the electrolyte to be 0.25 and 0.04 for PP separator without and with PIL coating, respectively. This suggests that the PIL layer reduces the contribution of the internal current due to cation transport. The use of PIL as a coating layer for commercial PP separator is a cost‐effective way to improve overall electrochemical performance of copper–lithium batteries. Compared to PP and polyacrylic acid(PAA)/PP separators, the PIL/PP membrane raises the Coulombic efficiency to 99% and decreases the average discharge voltage drop to about 0.09 V when the current density is increased from 0.1 to 1 mA cm−2. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is involved in the regulation of plant salt stress as a potential signaling molecule. This work investigated the effect of H2S on cucumber growth, photosynthesis, antioxidation, ion balance, and other salt tolerance pathways. The plant height, stem diameter, leaf area and photosynthesis of cucumber seedlings were significantly inhibited by 50 mmol·L−1 NaCl. Moreover, NaCl treatment induced superoxide anion (O2·−) and Na+ accumulation and affected the absorption of other mineral ions. On the contrary, exogenous spraying of 200 μmol·L−1 sodium hydrosulfide (NaHS) maintained the growth of cucumber seedlings, increased photosynthesis, enhanced the ascorbate–glutathione cycle (AsA–GSH), and promoted the absorption of mineral ions under salt stress. Meanwhile, NaHS upregulated SOS1, SOS2, SOS3, NHX1, and AKT1 genes to maintain Na+/K+ balance and increased the relative expression of MAPK3, MAPK4, MAPK6, and MAPK9 genes to enhance salt tolerance. These positive effects of H2S could be reversed by 150 mmol·L−1 propargylglycine (PAG, a specific inhibitor of H2S biosynthesis). These results indicated that H2S could mitigate salt damage in cucumber, mainly by improving photosynthesis, enhancing the AsA–GSH cycle, reducing the Na+/K+ ratio, and inducing the SOS pathway and MAPK pathway. [ABSTRACT FROM AUTHOR]

Light regulated ion transport across membranes is central to nature. Based on this, artificial nanofluidics with light driven ion transport behaviors has been developed for both fundamental study and practical applications. Here, we focus on recent progress in photothermal controlled ion transport systems and review the corresponding construction strategies in diverse photothermal nanofluidics with various dimensions and structures. We systematically emphasize the three underlying working principles including temperature gradient, water evaporation induced ion transport blockage, and evaporation gradient. On the basis of these fundamental research, photothermal regulated ion transport has been mainly introduced into ionic devices, desalination, and energy conversion. Furthermore, we provide some perspectives for the current challenges and future developments of this promising research field. We believe that this review could encourage further understanding and open the minds to develop new advances in this fertile research field. [ABSTRACT FROM AUTHOR]

Introduction: Smoking is one of the most important causes of cancer in humans. However, it has not been proven how long exposure to cigarette smoke is sufficient to induce cancerogenesis. Cigarette smoke can cause changes in ion and water transport and the maintenance of mucociliary transport. The conducted research concerned the assessment of changes in ion transport in rabbit tracheal specimens after 30 min of exposure to cigarette smoke. Materials and Methods: A modified Ussing chamber was used to measure the transepithelial electrical potential under stationary conditions (PD) and during mechanical stimulation (PDmin), and the transepithelial electrical resistance (R) in control and cigarette smoke-exposed tracheal fragments. Results: Significant changes in PD (−2.53 vs. −3.92 mV) and PDmin (−2.74 vs. −0.39 mV) were noted for the samples exposed to smoke, which can be associated with a rise in reactivity after applying a mechanical stimulus. In addition, the measured R (108 vs. 136 Ω/cm2) indicated no changes in the vitality of the samples, but an increase in their permeability to ions in the experimental conditions. Conclusions: A single 30-min exposure to cigarette smoke has been shown to be associated with increased permeability of the tracheal epithelium to ions and thus to substances emitted during smoking, which might be sufficient to create the possibility of initiating procarcinogenic processes. [ABSTRACT FROM AUTHOR]

In an effort to produce a lithium-ion battery for application in electronic devices, a gel polymer electrolyte (GPE) system was blended with poly(methyl methacrylate) (PMMA) and polylactic acid (PLA) doped with lithium bis(oxalato) borate (LiBOB) and incorporated with various compositions of 1-ethyl-3-methylimidazolium chloride (EMIM(Cl)) ranging from 0 wt.% to 24 wt.%. This study focused on the determination of free ions with the effect of the addition EMIM(Cl) in the PMMA/PLA-LiBOB through Fourier transform infrared (FTIR) spectroscopy and x-ray diffraction. The inclusion of EMIM(Cl) in the GPE systems was proven by the emergence of a new peak in the FTIR analysis. The changes that occurred in the FTIR spectra confirmed the complexation between the doped polymer blend with ionic liquid. The ionic liquid helps enhance the dissociation of the Li+ cation from the loosely bound Li+---BOB− and facilitates the transport of ions via the ion hopping mechanism. Consequently, the crystallinity of GPE samples becomes suppressed and reaches the optimum ionic conductivity up to 10−3 S cm−1 at room temperature for samples with 18 wt.% composition of EMIM(Cl). FTIR deconvolution shows that the ionic conductivity trend aligns with ion mobility and diffusion rates. The findings revealed that the present GPE-based PMMA/PLA–LiBOB doped with EMIM(Cl) has excellent potential to be applied as an energy storage device, especially a Li+ battery. [ABSTRACT FROM AUTHOR]

The design of ion‐selective membranes is the key towards efficient reverse electrodialysis‐based osmotic power conversion. The tradeoff between ion selectivity (output voltage) and ion permeability (output current) in existing porous membranes, however, limits the upgradation of power generation efficiency for practical applications. Thus, we provide the simple guidelines based on fundamentals of ion transport in nanofluidics for promoting osmotic power conversion. In addition, we discuss strategies for optimizing membrane performance through analysis of various material parameters in membrane design, such as pore size, surface charge, pore density, membrane thickness, ion pathway, pore order, and ionic diode effect. Lastly, a perspective on the future directions of membrane design to further maximize the efficiency of osmotic power conversion is outlined. [ABSTRACT FROM AUTHOR]

Although solid‐state batteries (SSBs) are high potential in achieving better safety and higher energy density, current solid‐state electrolytes (SSEs) cannot fully satisfy the complicated requirements of SSBs. Herein, a covalent organic framework (COF) with multi‐cationic molecular chains (COF‐MCMC) was developed as an efficient SSE. The MCMCs chemically anchored on COF channels were generated by nano‐confined copolymerization of cationic ionic liquid monomers, which can function as Li+ selective gates. The coulombic interaction between MCMCs and anions leads to easier dissociation of Li+ from coordinated states, and thus Li+ transport is accelerated. While the movement of anions is restrained due to the charge interaction, resulting in a high Li+ conductivity of 4.9×10−4 S cm−1 and Li+ transference number of 0.71 at 30 °C. The SSBs with COF‐MCMC demonstrate an excellent specific energy density of 403.4 Wh kg−1 with high cathode loading and limited Li metal source. [ABSTRACT FROM AUTHOR]

In recent decades, the development of dialysis techniques has greatly improved the survival rate of renal failure patients, and peritoneal dialysis is gradually showing dominance over hemodialysis. This method relies on the abundant membrane proteins in the peritoneum, avoiding the use of artificial semipermeable membranes, and the ion fluid transport is partly controlled by the protein nanochannels. Hence, this study investigated ion transport in these nanochannels by using molecular dynamics (MD) simulations and an MD Monte Carlo (MDMC) algorithm for a generalized protein nanochannel model and a saline fluid environment. The spatial distribution of ions was determined via MD simulations, and it agreed with that modeled via the MDMC method; the effects of simulation duration and external electronic fields were also explored to validate the MDMC algorithm. The specific atomic sequence within a nanochannel was visualized, which was the rare transport state during the ion transport process. The residence time was assessed through both methods to represent the involved dynamic process, and its values showed the temporal sequential order of different components in the nanochannel as follows: H2O > Na+ > Cl−. The accurate prediction using the MDMC method of the spatial and temporal properties proves its suitability to handle ion transport problems in protein nanochannels. [ABSTRACT FROM AUTHOR]

The degradation of drugs is a substantial problem since it affects the safety and effectiveness of pharmaceutical products, as well as their influence on the environment. A novel system of three potentiometric cross-sensitive sensors (using the Donnan potential (DP) as an analytical signal) and a reference electrode was developed for the analysis of UV-degraded sulfacetamide drugs. The membranes for DP-sensors were prepared by a casting procedure from a dispersion of perfluorosulfonic acid (PFSA) polymer, containing carbon nanotubes (CNTs), whose surface was preliminarily modified with carboxyl, sulfonic acid, or (3-aminopropyl)trimethoxysilanol groups. A correlation between the sorption and transport properties of the hybrid membranes and cross-sensitivity of the DP-sensor to sulfacetamide, its degradation product, and inorganic ions was revealed. The analysis of the UV-degraded sulfacetamide drugs using the multisensory system based on hybrid membranes with optimized properties did not require a pre-separation of the components. The limits of detection of sulfacetamide, sulfanilamide, and sodium were 1.8 × 10−7, 5.8 × 10−7, and 1.8 × 10−7 M. The relative errors of the determination of the components of the UV-degraded sulfacetamide drugs were 2–3% (at 6–8% relative standard deviation). PFSA/CNT hybrid materials provided the stable work of the sensors for at least one year. [ABSTRACT FROM AUTHOR]

Enhanced ionic current rectification induced by the concentration gradient has been reported recently owing to the development of asymmetric nanofluidic system, in particular graphene nanochannels. However, the reasons for the enhancement of ionic current rectification of graphene conical nanochannels are not well understood. Herein, a finite element model of a single graphene conical nanochannel is established to explore the fundamental mechanisms of the ionic current rectification. The model proves that the highest cation concentration caused by graphene is almost 42 times higher than the bulk ion concentration. Compared with the nongraphene model, the graphene with higher surface charge density can absorb more cation in the tip (the small pore) of graphene conical nanochannel. Besides, the nanoscale corner consisting of graphene membrane and the wall of the conical nanochannel is a semihermetic reservoir for cation accumulation. It demonstrates that the enhancement of ionic current rectification is mainly ascribed to the unique structure of the graphene nanochannel and the graphene membrane with a high surface charge density. This work provides a new mechanism explanation about the influence of graphene in ionic current rectification. [ABSTRACT FROM AUTHOR]

Nanofluidic reverse electrodialysis provides an attractive way to harvest osmotic energy. However, most attention was paid to monotonous membrane structure optimization to promote selective ion transport, while the role of external fields and relevant mechanisms are rarely explored. Here, we demonstrate a Kevlar‐toughened tungsten disulfide (WS2) composite membrane with bioinspired serosa‐mimetic structures as an efficient osmotic energy generator coupling light. As a result, the output power could be up to 16.43 W m−2 under irradiation, outperforming traditional two‐dimensional (2D) membranes. Both the experiment and simulation uncover that the generated photothermal and photoelectronic effects could synergistically promote the confined ion transport process. In addition, this membrane also possesses great anti‐fouling properties, endowing its practical application. This work paves new avenues for sustainable power generation by coupling solar energy. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is a group of heart disorders, which is a major cause of non-communicable disease-related mortalities worldwide. Myocardial infarction (MI) is an acute disorder due to the poor supply of oxygen and blood to the myocardium. MI is the foremost form of CVD, which is the primary cause of mortality worldwide. Objectives: Here, we intended to discover the ameliorative properties of the ponicidin against the isoproterenol (ISO)-stimulated MI in rats. Materials and Methods: About 85 mg/kg of ISO was administered to the rats to trigger the MI and then treated with 25 and 50 mg/kg of ponicidin. The body weight and heart weight of all rats were determined. The total protein, c-reactive protein (CRP), and uric acid levels were examined. The activities of cardiac function markers such as creatine kinase (CK), ALT, AST, and gamma-glutamyl transferase (GGT) were examined. The antioxidants such as glutathione (GSH), GST, and GPx were examined by the previous methods. The status of Na+/K+, Mg2+, and Ca2+ ATPase activities was assessed using kits. The status of Na+, K+, and Ca2+ ions and inflammatory makers such as TNF-α and IL-6 were investigated using respective kits. The histopathological analysis was performed on the heart tissues to detect the histological changes. Results: The results revealed that ponicidin increased body weight and decreased heart weight in MI rats. The status of CRP and uric acid was decreased and total protein was augmented in the ponicidin-treated MI rats. The AST, ALT, CK, and GGT activities were appreciably decreased in serum and elevated in the cardiac tissues of the ponicidin-administered MI rats. Furthermore, the ponicidin improved the antioxidant levels, decreased the TNF-α and IL-6, and regulated the Na+, K+, and Ca2+ ion transports in the MI rats. The activities of Na+/K+, Mg2+, and Ca2+ ATPase enzymes were remarkably increased in the heart tissues by the ponicidin-treated MI rats. Ponicidin treatment also ameliorated the ISO-stimulated histological alterations in the heart tissue of the MI rats. Conclusion: Ponicidin treatment appreciably improved the antioxidants, Na+/K+, Mg2+, and Ca2+ ATPase enzyme activities, decreased the inflammatory markers, and regulated the cardiac marker enzyme activities in the MI rats. Hence, it can be a talented therapeutic candidate in the future to treat MI. [ABSTRACT FROM AUTHOR]

[Display omitted] Memristor-based neuromorphic computing is promising for artificial intelligence. However, most of the reported memristors have limited linear computing states and consume large operation energy which hinder their applications. Herein, we report a memristor based on ionic two-dimensional CuInP 2 S 6 (2D CIPS), in which up to 1350 linear conductance states are achieved by controlling the migration of internal Cu ions in CIPS. In addition, the device shows a low operation current of ∼100 pA. Cu ions are proven to move along the electric field by in-situ scanning electron microscopy and energy dispersive spectroscopy measurements. Furthermore, complex signal transport among multiple neurons in the brain is imitated by 2D CIPS-based memristor arrays. Our results offer a new platform to fabricate high-performance memristors based on ion transport in 2D materials for neuromorphic computing. [ABSTRACT FROM AUTHOR]

Rechargeable magnesium batteries have attractive features as a post-lithium battery owing to their high volumetric capacity, safety, and low cost. However, the high charge density of Mg2+ causes sluggish interfacial charge transfer kinetics at the electrode/electrolyte interface. This paper is an attempt to optimize the electrochemical performance of a halogen-free liquid electrolyte (HFE)-based magnesium nitrate (Mg(NO3)2) and variable additive of succinonitrile (SN). A polymer layer interface (PLI) consisting of Mg (CF3SO3)2, polyvinylidene fluoride (PVDF), SN, and G4 has been introduced to isolate the Mg anode's surface from HFE in order to reduce the growth rate of the passivation layer at the surface of the Mg anode. The introduction of SN regulates the ionic conductivity, overpotential of Mg plating/stripping, and the ion transference number of the HFE. A prototype of the Mg/HFE_SN/S full cell delivers a high initial discharge/charge capacity of ~ 1200/500 mAh g−1 with a rapid capacity fade, while (Mg/PLI/HFE_SN/S) cell offers low capacity with long cycle life over (Mg/HFE_SN/S) counterpart. Postmortem analysis of sulfur electrodes at different electrochemical states reveals the reversible back and forth movement of Mg2+ ions in Mg/S cells via conversion reaction. [ABSTRACT FROM AUTHOR]

In recent years, the use of nanotechnology has shown great potential to enhance plant growth by combating stress tolerance. One of the major stress factors in agriculture is soil salinity, which adversely affects crop productivity and quality. The development of engineered nanoparticles (ENPs) has opened new avenues for alleviating salinity stress in plants. These ENPs usually made of biocompatible materials that have been shown to enhance plant growth and reduce salt stress-induced damage by improving their nutrient uptake, water balance, and anti-oxidative defense mechanisms. Several studies have reported the effectiveness of ENPs in enhancing plant growth and yield under salt stress conditions. For instance, silica nanoparticles were found to increase the chlorophyll content and photosynthetic efficiency of salt-stressed tomato plants, resulting in higher biomass and fruit yield. Similarly, chitosan nanoparticles were shown to increase the water-use efficiency of maize plants and reduce the accumulation of sodium ions in leaves under salt stress conditions. Furthermore, the ENPs can act as carriers for plant growth-promoting compounds, such as nutrients, hormones, or bioactive molecules, to enhance plant growth and stress tolerance.Despite the promising results, the use of ENPs in agriculture raises concerns about their potential environmental impacts and safety for human health. The fate and transport of ENPs in soil and water systems, as well as their potential toxicity to non-target organisms, need to be carefully evaluated. This review analyzes the use of ENPs as a tool for mitigating salinity stress in plants and offers a promising strategy that requires further research and development to optimize their efficacy and safety in agricultural applications.

Abstract Nanochannel‐based ion transport is an important field of study in various disciplines, including physics, chemistry, energy, materials science, biology, and earth science. The unique features of natural nanochannels have inspired numerous innovative designs that seek to achieve high ion permeability, selectivity, and rectification. A notable example is osmotic energy conversion, which harvests sustainable salinity‐gradient energy to generate electricity without moving parts, noise, or carbon emissions and thus serves as a promising alternative to traditional fossil fuel utilization. This review focuses on the fundamental principles, regulatory methods, and practical applications of nanochannel‐based ion transport for osmotic energy conversion. The physical mechanisms of ion transport and the intriguing phenomena of ion behaviors in nanoconfined spaces are discussed first, followed by a thorough examination of the overall process of osmotic power generation from mathematical, numerical, parametric, first‐principles, molecular simulation, and modeling perspectives. Strategies for enhancing the osmotic performance are then discussed to overcome the trade‐off between ion selectivity and ion flux, including the theoretical design of nanochannel geometry and electrification, experimental optimization of nanoporous membranes, and electrolyte thermal enhancement. The existing challenges and opportunities for the future development of nanochannel‐based ion transport and osmotic power generation are addressed at the end.

Poly(ethylene oxide)-b-polyhedral oligomeric silsesquioxane (PEO–POSS) mixed with lithium bis(trifluoromethanesulfonyl)imide salt is a nanostructured hybrid organic–inorganic block copolymer electrolyte that may enable lithium metal batteries. The synthesis and characteristics of three PEO–POSS block copolymer electrolytes which only differ by their POSS silica cage substituents (ethyl, isobutyl, and isooctyl) is reported. Changing the POSS monomer structure results in differences in both thermodynamics and ion transport. All three neat polymers exhibit lamellar morphologies. Adding salt results in the formation of a disordered window which closes and gives way to lamellae at higher salt concentrations. The width of disordered window decreases with increasing length of the POSS alkyl chain substituent from ethyl to isobutyl and is absent in the isooctyl sample. Rheological measurements demonstrate good mechanical rigidity when compared with similar all-organic block copolymers. While salt diffusion coefficient and current ratio are unaffected by substituent length, ionic conductivity increases as the length of the alkyl chain substituent decreases: the ethyl substituent is optimal for ion transport. This is surprising because conventional wisdom suggests that ion transport occurs primarily in the PEO-rich domains, that is, ion transport should be unaffected by substituent length after accounting for the minor change in conducting phase volume fraction. © 2020 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2020 © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 363–371.

Chemiosmosis and substrate-level phosphorylation are the 2 mechanisms employed to form the biological energy currency adenosine triphosphate (ATP). During chemiosmosis, a transmembrane electrochemical ion gradient is harnessed by a rotary ATP synthase to phosphorylate adenosine diphosphate to ATP. In microorganisms, this ion gradient is usually composed of [Formula: see text], but it can also be composed of Na+ Here, we show that the strictly anaerobic rumen bacterium Pseudobutyrivibrio ruminis possesses 2 ATP synthases and 2 distinct respiratory enzymes, the ferredoxin:[Formula: see text] oxidoreductase (Rnf complex) and the energy-converting hydrogenase (Ech complex). In silico analyses revealed that 1 ATP synthase is [Formula: see text]-dependent and the other Na+-dependent, which was validated by biochemical analyses. Rnf and Ech activity was also biochemically identified and investigated in membranes of P. ruminis Furthermore, the physiology of the rumen bacterium and the role of the energy-conserving systems was investigated in dependence of 2 different catabolic pathways (the Embden-Meyerhof-Parnas or the pentose-phosphate pathway) and in dependence of Na+ availability. Growth of P. ruminis was greatly stimulated by Na+, and a combination of physiological, biochemical, and transcriptional analyses revealed the role of the energy conserving systems in P. ruminis under different metabolic scenarios. These data demonstrate the use of a 2-component ion circuit for [Formula: see text] bioenergetics and a 2nd 2-component ion circuit for Na+ bioenergetics in a strictly anaerobic rumen bacterium. In silico analyses infer that these 2 circuits are prevalent in a number of other strictly anaerobic microorganisms.

LacY catalyzes accumulation of galactosides against a concentration gradient by coupling galactoside and H+ transport (i.e., symport). While alternating access of sugar- and H+-binding sites to either side of the membrane is driven by binding and dissociation of sugar, the electrochemical H+ gradient ([Formula: see text]) functions kinetically by decreasing the Km for influx 50- to 100-fold with no change in Kd The affinity of protonated LacY for sugar has an apparent pK (pKapp) of ∼10.5, due specifically to the pKa of Glu325, a residue that plays an irreplaceable role in coupling. In this study, rates of lactose/H+ efflux were measured from pH 5.0 to 9.0 in the absence or presence of a membrane potential (ΔΨ, interior positive), and the effect of the imposed ΔΨ on the kinetics of efflux was also studied in right-side-out membrane vesicles. The findings reveal that [Formula: see text] induces an asymmetry in the transport cycle based on the following observations: 1) the efflux rate of WT LacY exhibits a pKapp of ∼7.2 that is unaffected by the imposed ΔΨ; 2) ΔΨ increases the rate of efflux at all tested pH values, but enhancement is almost 2 orders of magnitude less than observed for influx; 3) mutant Glu325 - Ala does little or no efflux in the absence or presence of ΔΨ, and ambient pH has no effect; and 4) the effect of ΔΨ (interior positive) on the Km for efflux is almost insignificant relative to the 50- to 100-fold decrease in the Km for influx driven by ΔΨ (interior negative).

The lumenal pH of an organelle is one of its defining characteristics and central to its biological function. Experiments have elucidated many of the key pH regulatory elements and how they vary from compartment-to-compartment, and continuum mathematical models have played an important role in understanding how these elements (proton pumps, counter-ion fluxes, membrane potential, buffering capacity, etc.) work together to achieve specific pH setpoints. While continuum models have proven successful in describing ion regulation at the cellular length scale, it is unknown if they are valid at the subcellular level where volumes are small, ion numbers may fluctuate wildly, and biochemical heterogeneity is large. Here, we create a discrete, stochastic (DS) model of vesicular acidification to answer this question. We used this simplified model to analyze pH measurements of isolated vesicles containing single proton pumps and compared these results to solutions from a continuum, ordinary differential equations (ODE)-based model. Both models predict similar parameter estimates for the mean proton pumping rate, membrane permeability, etc., but, as expected, the ODE model fails to report on the fluctuations in the system. The stochastic model predicts that pH fluctuations decrease during acidification, but noise analysis of single-vesicle data confirms our finding that the experimental noise is dominated by the fluorescent dye, and it reveals no insight into the true noise in the proton fluctuations. Finally, we again use the reduced DS model explore the acidification of large, lysosome-like vesicles to determine how stochastic elements, such as variations in proton-pump copy number and cycling between on and off states, impact the pH setpoint and fluctuations around this setpoint.

The biophysical environment of membrane phospholipids affects structure, function, and stability of membrane-bound proteins.1,2 Obesity can disrupt membrane lipids, and in particular, alter the activity of sarco/endoplasmic reticulum (ER/SR) Ca2+-ATPase (SERCA) to affect cellular metabolism.3-5 Recent evidence suggests that transport efficiency (Ca2+ uptake / ATP hydrolysis) of skeletal muscle SERCA can be uncoupled to increase energy expenditure and protect mice from diet-induced obesity.6,7 In isolated SR vesicles, membrane phospholipid composition is known to modulate SERCA efficiency.8-11 Here we show that skeletal muscle SR phospholipids can be altered to decrease SERCA efficiency and increase whole-body metabolic rate. The absence of skeletal muscle phosphatidylethanolamine (PE) methyltransferase (PEMT) promotes an increase in skeletal muscle and whole-body metabolic rate to protect mice from diet-induced obesity. The elevation in metabolic rate is caused by a decrease in SERCA Ca2+-transport efficiency, whereas mitochondrial uncoupling is unaffected. Our findings support the hypothesis that skeletal muscle energy efficiency can be reduced to promote protection from obesity.

Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration. Studies on Piezo1 have largely focused on transduction of "outside-in" mechanical forces, and its response to internal, cell-generated forces remains poorly understood. Here, using measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that cellular traction forces generate spatially-restricted Piezo1-mediated Ca2+ flickers in the absence of externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched near force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that mobility allows Piezo1 channels to explore a large number of mechanical microdomains and thus respond to a greater diversity of mechanical cues.

The hypothalamus contains a number of nuclei that subserve a variety of functions, including generation of circadian rhythms, regulation of hormone secretion and maintenance of homeostatic levels for a variety of physiological parameters. Within the hypothalamus, γ-amino-butyric acid (GABA) is one of the major neurotransmitters responsible for cellular communication. Although GABA most commonly serves as an inhibitory neurotransmitter, a growing body of evidence indicates that it can evoke post-synaptic excitation as a result of the active regulation of intracellular chloride concentration. In this review, we consider the evidence for this ionic plasticity of GABAergic synaptic transmission in five distinct cases in hypothalamic cell populations. We argue that this plasticity serves as part of the functional response to or is at least associated with dehydration, lactation, hypertension and stress. As such, GABA excitation should be considered as part of the core homeostatic mechanisms of the hypothalamus.

Reactive oxygen species such as H2O2 are believed to play a prominent role in the injury and loss of transport function that affect the intestinal epithelium in inflammatory conditions such as inflammatory bowel diseases. Defects in intestinal epithelial ion transport regulation contribute to dysbiosis and inflammatory phenotypes. We previously showed that H2O2 inhibits Ca2+-dependent Cl- secretion across intestinal epithelial cells (IECs) via a phosphatidylinositol 3-kinase (PI3K)- and extracellular signal-regulated kinase (ERK)-dependent mechanism that occurs, at least in part, through inhibition of the basolateral Na+-K+-2Cl- cotransporter NKCC1. NKCC1 governs Cl- entry into crypt IECs and thus plays a critical role in maintaining the driving force for Cl- secretion. Electrolyte transport consumes large amounts of cellular energy, and direct pharmacological activation of the cellular energy sensor AMP-activated protein kinase (AMPK) has been shown to inhibit a number of ion transport proteins. Here, we show that H2O2 activates AMPK in human IEC lines and ex vivo human colon. Moreover, we demonstrate that the inhibitory effect of H2O2 on Ca2+-dependent Cl- secretion and NKCC1 activity is AMPK-dependent. This inhibitory effect is associated with a physical interaction between AMPK and NKCC1, as well as increased phosphorylation (Thr212,217) of NKCC1, without causing NKCC1 internalization. These data identify a key role for AMPK-NKCC1 interaction as a point of convergence for suppression of colonic epithelial ion transport by inflammatory reactive oxygen species.NEW & NOTEWORTHY H2O2 inhibition of intestinal epithelial Ca2+-dependent Cl- secretion involves recruitment of AMP-activated protein kinase (AMPK) downstream of ERK and phosphatidylinositol 3-kinase signaling pathways, physical interaction of AMPK with the Na+-K+-2Cl- cotransporter NKCC1, and AMPK-dependent suppression of NKCC1-mediated electrolyte influx without causing NKCC1 internalization. It is intriguing that, in human intestinal epithelial cell lines and human colon, H2O2 activation of AMPK increased phosphorylation of NKCC1 residues required for promoting, not inhibiting, NKCC1 activity. These data identify an elevated complexity of AMPK regulation of NKCC1 in the setting of an inflammatory stimulus.

The mitochondrial ADP/ATP carrier (AAC) is a major transport protein of the inner mitochondrial membrane. It exchanges mitochondrial ATP for cytosolic ADP and controls cellular production of ATP. In addition, it has been proposed that AAC mediates mitochondrial uncoupling, but it has proven difficult to demonstrate this function or to elucidate its mechanisms. Here we record AAC currents directly from inner mitochondrial membranes from various mouse tissues and identify two distinct transport modes: ADP/ATP exchange and H+ transport. The AAC-mediated H+ current requires free fatty acids and resembles the H+ leak via the thermogenic uncoupling protein 1 found in brown fat. The ADP/ATP exchange via AAC negatively regulates the H+ leak, but does not completely inhibit it. This suggests that the H+ leak and mitochondrial uncoupling could be dynamically controlled by cellular ATP demand and the rate of ADP/ATP exchange. By mediating two distinct transport modes, ADP/ATP exchange and H+ leak, AAC connects coupled (ATP production) and uncoupled (thermogenesis) energy conversion in mitochondria.

A key assumption of optogenetics is that light only affects opsin-expressing neurons. However, illumination invariably heats tissue, and many physiological processes are temperature-sensitive. Commonly used illumination protocols increased the temperature by 0.2-2 °C and suppressed spiking in multiple brain regions. In the striatum, light delivery activated an inwardly rectifying potassium conductance and biased rotational behavior. Thus, careful consideration of light-delivery parameters is required, as even modest intracranial heating can confound interpretation of optogenetic experiments.

Although small airways account for the largest fraction of the total conducting airway surfaces, the epithelial fluid and electrolyte transport in small, native airway epithelia has not been well characterized. Investigations have been limited, no doubt, by the complex tissue architecture as well as by its inaccessibility, small dimensions, and lack of applicable assays, especially in human tissues. To better understand how the critically thin layer of airway surface liquid (ASL) is maintained, we applied a "capillary"-Ussing chamber (area ≈1 mm2) to measure ion transport properties of bronchioles with diameters of ~2 mm isolated from resected specimens of excised human lungs. We found that the small human airway, constitutively and concurrently, secretes and absorbs fluid as observed in porcine small airways (50). We found that the human bronchiolar epithelium is also highly anion selective and constitutively secretes bicarbonate ( HCO3- ), which can be enhanced pharmacologically by cAMP as well as Ca2+-mediated agonists. Concurrent secretion and absorption of surface liquid along with HCO3- secretion help explain how the delicate volume of the fluid lining the human small airway is physiologically buffered and maintained in a steady state that avoids desiccating or flooding the small airway with ASL.

Two TMEM16 family members, TMEM16A and TMEM16F, have different ion transport properties. Upon activation by intracellular Ca2+, TMEM16A-a Ca2+-activated Cl- channel-is more selective for anions than cations, whereas TMEM16F-a phospholipid scramblase-appears to transport both cations and anions. Under saturating Ca2+ conditions, the current-voltage (I-V) relationships of these two proteins also differ; the I-V curve of TMEM16A is linear, while that of TMEM16F is outwardly rectifying. We previously found that mutating a positively charged lysine residue (K584) in the ion transport pathway to glutamine converted the linear I-V curve of TMEM16A to an outwardly rectifying curve. Interestingly, the corresponding residue in the outwardly rectifying TMEM16F is also a glutamine (Q559). Here, we examine the ion transport functions of TMEM16 molecules and compare the roles of K584 of TMEM16A and Q559 of TMEM16F in controlling the rectification of their respective I-V curves. We find that rectification of TMEM16A is regulated electrostatically by the side-chain charge on the residue at position 584, whereas the charge on residue 559 in TMEM16F has little effect. Unexpectedly, mutation of Q559 to aromatic amino acid residues significantly alters outward rectification in TMEM16F. These same mutants show reduced Ca2+-induced current rundown (or desensitization) compared with wild-type TMEM16F. A mutant that removes the rundown of TMEM16F could facilitate the study of ion transport mechanisms in this phospholipid scramblase in the same way that a CLC-0 mutant in which inactivation (or closure of the slow gate) is suppressed was used in our previous studies.