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The bottom current is an important component of the three-dimensional ocean circulation, which is of significance for the safeties of ocean bottom engineering and facilities, the research on sediment and pollutant transports, and the ecological environment. Due to the lack of observation data, research on the bottom current in the South China Sea (SCS) has been limited. This study systematically analyzes bottom currents from 0.5 to 5 m above the seafloor based on 20-month-long mooring observations on the shelf slope west of the Dongsha Atoll. The spectral analysis results indicate that currents induced by the internal tides and the internal solitary waves (ISWs) comprise dominant constituents of bottom currents with velocity amplitudes up to O(50–90) cm/s. Dominant internal tide-induced bottom currents of the velocity amplitude of O(50) cm/s occupy 53% of the total horizontal kinetic energy. The pulsating ISW-induced bottom currents reach a maximum amplitude of 93 cm/s, which has intrinsic relation to the amplitude of the ISWs, according to the soliton propagation speed solutions of the Korteweg–De Vries (KdV) equation. The background bottom current is strongest in winter, followed by spring, and weak in summer and autumn, which is closely correlated with the behavior of mesoscale eddies. These results are of significance for understanding the dynamics of the bottom boundary layer.

The effect of pressure on positive and negative streamer propagation in a mineral transformer oil is studied in an 80 mm point-plane gap under step voltage. Increased pressure causes reduced stopping length for non-breakdown streamers, higher breakdown voltage, reduced background current, reduced branching in positive streamers and virtually no change in negative streamer shape. The velocities and acceleration voltages are close to being independent of pressure, indicating that the velocity controlling mechanisms take place in the liquid phase. Amplitude and frequency of small current pulses (probably small "reilluminations") during negative 1st mode is reduced with increasing pressure, but the effect on reilluminations during 2nd and 3rd mode is small in both polarities. [ABSTRACT FROM AUTHOR]

Pyrethroid insecticides are widely used for pest control in agriculture or in human public health commonly as a topical treatment for scabies and head lice. Exposure to pyrethroids such as permethrin or tetramethrin (TM) causes sensory alterations such as transient pain, burning, stinging sensations, and paraesthesias. Despite the well-known effects of pyrethroids on sodium channels, actions on other channels that control sensory neuron excitability are less studied. Given the role of 2-pore domain potassium (K2P) channels in modulating sensory neuron excitability and firing, both in physiological and pathological conditions, we examined the effect of pyrethroids on K2P channels mainly expressed in sensory neurons. Through electrophysiological and calcium imaging experiments, we show that a high percentage of TM-responding neurons were nociceptors, which were also activated by TRPA1 and/or TRPV1 agonists. This pyrethroid also activated and enhanced the excitability of peripheral saphenous nerve fibers. Pyrethroids produced a significant inhibition of native TRESK, TRAAK, TREK-1, and TREK-2 currents. Similar effects were found in transfected HEK293 cells. At the behavioral level, intradermal TM injection in the mouse paw produced nocifensive responses and caused mechanical allodynia, demonstrating that the effects seen on nociceptors in culture lead to pain-associated behaviors in vivo. In TRESK knockout mice, pain-associated behaviors elicited by TM were enhanced, providing further evidence for a role of this channel in preventing excessive neuronal activation. Our results indicate that inhibition of K2P channels facilitates sensory neuron activation and increases their excitability. These effects contribute to the generation of paraesthesias and pain after pyrethroid exposure. [ABSTRACT FROM AUTHOR]

Background inward sodium current (I B,Na ) that influences cardiac pacemaking has been comparatively under-investigated. The aim of this study was to determine for the first time the properties and role of I B,Na in cells from the heart's secondary pacemaker, the atrioventricular node (AVN). Myocytes were isolated from the AVN of adult male rabbits and mice using mechanical and enzymatic dispersion. Background current was measured using whole-cell patch clamp and monovalent ion substitution with major voltage- and time-dependent conductances inhibited. In the absence of a selective pharmacological inhibitor of I B,Na , computer modelling was used to assess the physiological contribution of I B,Na . Net background current during voltage ramps was linear, reversing close to 0 mV. Switching between Tris- and Na + -containing extracellular solution in rabbit and mouse AVN cells revealed an inward I B,Na , with an increase in slope conductance in rabbit cells at − 50 mV from 0.54 ± 0.03 to 0.91 ± 0.05 nS (mean ± SEM; n = 61 cells). I B,Na magnitude varied in proportion to [Na + ] o . Other monovalent cations could substitute for Na + (Rb + > K + > Cs + > Na + > Li + ). The single-channel conductance with Na + as charge carrier estimated from noise-analysis was 3.2 ± 1.2 pS (n = 6). Ni 2 + (10 mM), Gd 3 + (100 μM), ruthenium red (100 μM), or amiloride (1 mM) produced modest reductions in I B,Na . Flufenamic acid was without significant effect, whilst La 3 + (100 μM) or extracellular acidosis (pH 6.3) inhibited the current by > 60%. Under the conditions of our AVN cell simulations, removal of I B,Na arrested spontaneous activity and, in a simulated 1D-strand, reduced conduction velocity by ~ 20%. I B,Na is carried by distinct low conductance monovalent non-selective cation channels and can influence AVN spontaneous activity and conduction. [ABSTRACT FROM AUTHOR]

The atrioventricular node (AVN) of the cardiac conduction system coordinates atrial-ventricular excitation and can act as a subsidiary pacemaker. Recent evidence suggests that an inward background sodium current, IB,Na, carried by nonselective cation channels (NSCCs), contributes to AVN cell pacemaking. The study of the physiological contribution of IB,Na has been hampered, however, by a lack of selective pharmacological antagonists. This study investigated effects of the NSCC inhibitor SKF-96365 on spontaneous activity, IB,Na, and other ionic currents in AVN cells isolated from the rabbit. Whole-cell patch-clamp recordings of action potentials (APs) and ionic currents were made at 35-37°C. A concentration of 10 μmol/L SKF-96365 slowed spontaneous action potential rate by 13.9 ± 5.3% ( n = 8) and slope of the diastolic depolarization from 158.1 ± 30.5 to 86.8 ± 30.5 mV sec−1 ( P < 0.01; n = 8). Action potential upstroke velocity and maximum diastolic potential were also reduced. Under IB,Na-selective conditions, 10 μmol/L SKF-96365 inhibited IB,Na at −50 mV by 36.1 ± 6.8% ( n = 8); however, effects on additional channel currents were also observed. Thus, the peak L-type calcium current ( ICa,L) at +10 mV was inhibited by 38.6 ± 8.1% ( n = 8), while the rapid delayed rectifier current, IKr, tails at −40 mV following depolarization to +20 mV were inhibited by 55.6 ± 4.6% ( n = 8). The hyperpolarization-activated current, If, was unaffected by SKF-96365. Collectively, these results indicate that SKF-96365 exerts a moderate inhibitory effect on IB,Na and slows AVN cell pacemaking. However, additional effects of the compound on ICa,L and IKr confound the use of SKF-96365 to dissect out selectively the physiological role of IB,Na in the AVN. [ABSTRACT FROM AUTHOR]

Based on modifications of the observed background parabolic current in upper layer of the northeastern South China Sea (SCS), the effects of eight kinds of background currents on the characteristics and energy conversion of internal solitary waves (ISWs) are investigated by an Internal Gravity Wave (IGW) model. It is found that, although the background current has little effect on the number of the generated ISWs, it reduces the resulted phase speed of ISW. When the background parabolic current appears with its lower boundary near or above the main thermocline, the ISW amplitude and the depth of the isopycnal undergoing maximum displacement increase; when the background parabolic current curvature is reduced, the ISW amplitude and the ratio of baroclinic to barotropic energy reduce, whilst the phase speed of ISW, the baroclinic energy, and the ratio of baroclinic kinetic energy (KE) to available potential energy (APE) increase; when the lower boundary of background parabolic current extends down to the seabed and the background current curvature is reduced, the ISW amplitude and phase speed decrease, whilst the barotropic kinetic energy, the baroclinic energy and the ratio of KE to APE increase. At a whole depth, when the lower background current curvature is reduced and the upper current curvature is increased, the ISW amplitude, and phase speed, the ratio of baroclinic to barotropic energy, the baroclinic energy, and the ratio of KE to APE all increase. [ABSTRACT FROM AUTHOR]

The spatial-temporal characteristics of internal tides (ITs) in the southwest Luzon Strait are examined, based on 9-month mooring current records from autumn 2008 to summer 2009. The results of spectral analysis show that the ITs in diurnal and semidiurnal frequencies are prominent at the mooring site, especially for the clockwise rotary component. The diurnal ITs are mostly dominated by the first mode except for that in spring when the second mode is relatively predominant. The semidiurnal ITs display a variable multimodal structure. Moreover, an apparent difference is detected in the kinetic energy of diurnal ITs. The energy is strongest in winter, and followed by that in summer, whereas the value is smallest in spring and autumn. It is suggested that the incoherent motions are responsible for the significant seasonal variations of diurnal ITs, reflecting interaction between diurnal ITs and the varying background conditions. However, the semidiurnal ITs are independent of seasonal change, whose energy is smaller and only one-third of the diurnal energy in winter. Nevertheless, the abnormal variations of semidiurnal ITs are also related to the variable background conditions. The incoherent semidiurnal constituent accounts for about 37% of the total semidiurnal tidal kinetic energy, but the diurnal tidal motions contain fewer incoherent component (22.2%). [ABSTRACT FROM AUTHOR]

Abstract: Two-pore-domain K+ (K2P) channels are highly expressed in neurons and cardiac myocytes. In this study we investigated the potency of the antidepressant fluoxetine to inhibit brain and cardiac K2P channels, TREK-1, TASK-1 and THIK-1. Maximal sensitivity was detected for TREK-1, which was inhibited by 77% when expressed in HEK-293 cells and Xenopus oocytes. Alternative translation initiation (ATI) generates two different protein products from a single transcript of TREK-1. Electrophysiological analysis of two polypeptides engineered by mutagenesis (TREK-1[M53I], TREK-1[ΔN52]) revealed reduced current amplitude and K+ selectivity of the truncated TREK-1 isoform. The sensitivity of TREK-1[ΔN52] to fluoxetine decreased by 70%, indicating that the first 52 amino acids are essential for TREK-1 sensitivity to this drug. [Copyright &y& Elsevier]

three-layer model of an inviscid incompressible fluid is considered in a quasigeostrophic approximation within the concept of background currents. A singular topographic obstacle yields the formation of a vortical motion in the layers. It is always present in the lower layer, while in the upper and middle layers it can be observed only at certain velocities of the external flows. Three current functions describing a singular topographic flow in the lower layer and two regular flows in the upper layer are obtained. In case of a nonstationary harmonic perturbation of the external flow, chaotic particle transport is possible in these flows. This paper analyzes the chaotic properties of this model. Depending on the type of unperturbed frequency curves of the fluid particle revolution is determined by the model parameters (stratification) and the incident flow, the patterns of the chaotic transport will substantially differ. Two of the limiting dependences of the revolution frequency are determined, namely, the dependence for a singular vortex and that for a regular vortex with the smallest area. Other dependences are intermediate ones. Two limiting types of revolution frequencies determine the two different scenarios of chaotic advection. [ABSTRACT FROM AUTHOR]

The electrochemical behavior of polycrystalline diamond films of different thickness (0.5-7 μm), grown by hot-filament CVD method, was studied by electrochemical impedance spectroscopy and cyclic voltammetry. The differential capacitance, background current, and potential window were measured in supporting electrolyte solution; the electrochemical kinetics, in [Fe(CN)] model redox system. With the increasing of the films thickness, the crystallite size increased; both the differential capacitance and background current in the indifferent electrolyte, as well as the transfer coefficients in the redox system, decreased; thus, the diamond electrode becomes as if less reversible. The effect of the films' thickness is reduced to that of nondiamond (amorphous) carbon contribution from intercrystalline boundaries on the electrochemical behavior of the polycrystalline diamond electrodes. [ABSTRACT FROM AUTHOR]

The transient receptor potential (TRP) family of ion channels comprises more than 50 cation-permeable channels expressed throughout the animal kingdom. TRPs can be grouped into 7 main subfamilies according to structural homology: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), TRPA (ankyrin), and TRPN (NO mechanopotential). During the past 20 years, the cloning and characterization after reexpression of most members of these cation channels have led to a plethora of data and more recently to some understanding of their roles in various cells and tissues. Specifically in the heart, TRPs are known to be involved in various diseases, including hypertrophy, heart failure, and arrhythmia. The later part of this review focuses on the potential contribution of TRPs to cardiac rhythm and their potential proarrhythmic effects. Furthermore, several neurotransmitters that activate the formation of diacylglycerol could modulate cardiac rhythm or, like ATP, induce arrhythmia. La famille de canaux ioniques à TRP, potentiel récepteur transitoire, comprend plus de 50 canaux perméables aux cations, exprimés dans le règne animal. Les TRP peuvent être divisés en sept sous-familles sur la base des homologies structurelles : groupe TRPC « canonique », groupe TRPV « vanilloïde », groupe TRPM « mélastanine », groupe TRPP polycystine », groupe TRPML « mucolipine », groupe TRPA « ankyrine » et groupe « TRPN NOMP ». Le clonage et la caractérisation après la réexpression de la plupart des membres de ces canaux cationiques au cours des 20 dernières années ont donné lieu à une richesse de données et, plus récemment, à une meilleure compréhension de leurs rôles dans divers tissus et cellules. Dans le cœur en particulier, les TRP sont impliqués dans diverses maladies dont l’hypertrophie, l’insuffisance cardiaque et l’arythmie. La dernière partie de ce chapitre est axée sur la contribution potentielle des TRP au rythme cardiaque et sur leurs possibles effets proarythmiques. De plus, plusieurs neurotransmetteurs qui activent la formation de diacylglycerol pourraient moduler le rythme cardiaque ou, comme l’ATP, provoquer l’arythmie. [ABSTRACT FROM AUTHOR]

An amperometric glucose biosensor with immobilized glucose oxidase enzyme is developed and its performance is investigated for the analysis of glucose concentration. A systematic method to find the background current in an amperometric biosensor is proposed, and the procedure for the minimization of the current has been reported. Tests were conducted for the analysis of glucose in different fruit juices. The current generated in an enzyme based amperometric biosensor depends on both the sensing current and the background current. The performance of amperometric biosensor is better when it is operated at optimized operating conditions and with minimum background current. The effect of current caused by the interference contained in the physiological fluids (uric acid and ascorbic acid) is found negligible. It has been found that the thickness of the membrane will affect the response time and the increase in background current will affect the sensitivity. [ABSTRACT FROM AUTHOR]

Abstract: This report describes a hitherto unreported anionic background current from human atrial cardiomyocytes. Under whole-cell patch-clamp with anion-selective conditions, an outwardly rectifying anion current (I ANION) was observed, which was larger with iodide than nitrate, and with nitrate than chloride as charge carrier. In contrast with a previously identified background anionic current from small mammal cardiomyocytes, I ANION was not augmented by the pyrethroid tefluthrin (10μM); neither was it inhibited by hyperosmolar external solution nor by DIDS (200μM); thus I ANION was not due to basal activity of volume-sensitive anion channels. I ANION was partially inhibited by the Cl− channel blockers NPPB (50μM) and Gly H-101 (30μM). Incorporation of I ANION into a human atrial action potential (AP) simulation led to depression of the AP plateau, accompanied by alterations to plateau inward calcium current, and to AP shortening at 50% but not 90% of complete repolarization, demonstrating that I ANION can influence the human atrial AP profile. [Copyright &y& Elsevier]

Ten genes with essential structural features of two-pore domain potassium channels were identified in the genome of Drosophila melanogaster. Two Drosophila two-pore domain potassium subunits displayed substantial amino acid similarity to human TWIK-related acid-sensitive K+ (TASK) channels (38–43%), whereas all others were less than 26% similar to any human homolog. The cDNAs of Drosophila TASK (dTASK)-6 and dTASK-7 channels were isolated from adult fruit flies. In Northern blots dTASK transcripts were found predominantly in the head fraction of adult flies and whole-mount brain in situ hybridizations showed strongly overlapping expression patterns of both dTASK isoforms in the antennal lobes. When heterologously expressed in Drosophila Schneider 2 cells, dTASK-6 gave rise to rapidly activating K+-selective currents that steeply depended on external pH. Structural elements in the extracellular M1–P1 loop of dTASK-6 were found to be involved in proton sensation. In contrast to mammalian TASK channels, the pH sensitivity was independent of extracellular histidines adjacent to the GYG selectivity filter (His98). As revealed by mutational analysis, functional expression of dTASK-7 was prevented by two nonconserved amino acids (Ala92-Met93) in the pore domain. When these two residues were replaced by conserved Thr92-Thr93, typical K+-selective leak currents were generated that were insensitive to changes in external pH. Nonfunctional wildtype dTASK-7 channels appeared to form heteromeric assemblies with dTASK-6. Following cotransfection of dTASK-6 and wildtype dTASK-7 (or when engineered as concatemers), K+ currents were observed that were smaller in amplitude, harbored slower activation kinetics and were considerably less inhibited by local anesthetics as compared with dTASK-6. Thus, pore-loop residues in dTASK-7 changed functional and pharmacological properties in heteromeric dTASK channels. [ABSTRACT FROM AUTHOR]

Abstract: A cDNA encoding a two-pore domain potassium (K2p) channel subunit, AcK2p2, was cloned from the CNS of the marine opisthobranch Aplysia californica. This is the second K2p subunit to be identified in molluscs. Like the K2p subunit cloned previously from Aplysia, AcK2p2 appears to be more closely related to human K2p channels than to any from Drosphila melanogaster or Caenorhabditis elegans. However, the overall identity is much lower (24% with human TALK-1) and phylogenetic analysis indicates that AcK2p2 cannot be grouped into any established mammalian subclass. We analyzed the distribution of this channel by in situ hybridization in whole mount preparations of the CNS. Less than a dozen of the approximately 20,000 neurons in the CNS expressed AcK2p2 at high levels, with the consistently intense labeling seen in a single bilaterally symmetrical pair of pedal neurons. The neuron-specific expression pattern seen for this channel is consistent with data from a variety of organisms that implicate K2p channels as determinants of neuronal phenotype and function. [Copyright &y& Elsevier]

Endogenous pacemaker properties have been proposed to generate rhythmic activity underlying many behaviors including respiration. For pacemakers to generate regenerative bursting, background currents maintain their membrane potential (Vm) within a range where bi-stable properties are expressed, thereby stabilizing rhythmogenesis. We previously found that the baseline Vm of respiratory pacemakers is stabilized against hyperpolarizing shifts in their Vm. In response to prolonged hyperpolarizing current injection synaptically isolated respiratory pacemakers steadily depolarize and resume bursting, suggesting a stabilizing background current is involved. What is the ionic basis of this background current in respiratory pacemakers? Here we demonstrate that in low-[Na+]o ACSF, synaptically isolated respiratory pacemakers hyperpolarized and remained outside the bursting window, but could burst upon depolarizing current injection. These data suggest that pacemakers possess a background sodium current that is necessary to bring their Vm into a bursting range. Low-[Na+]o ACSF also abolished the depolarizing shift evoked during prolonged hyperpolarizing current injection, and bursting did not resume. This depolarizing shift persisted in the presence of Ih-current blockers, but was abolished in tetrodotoxin. Although, under control conditions, the Vm of synaptically isolated respiratory pacemaker neurons was not significantly affected when [K+]o was changed from 3 to 8 m M, the Vm is altered when [K+]o was raised in low-[Na+]o ACSF. Thus, current-clamp studies suggest that respiratory pacemaker neurons possess a background sodium current that maintains their membrane potential within a range where they express bursting, thereby stabilizing rhythmogenesis. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 481-489, 2004 [ABSTRACT FROM AUTHOR]

Single sino-atrial cells from rabbit heart were voltage-clamped using the whole-cell configuration of the patch clamp technique under conditions in which most of the ionic and exchange currents known in pacemaker cardiac cells were minimized. Extracellular angiotensin II (AII) activated a time-independent background current. The current-voltage relation of this current showed an outward rectification. The reversal potential was −20 mV with 156 m m Cl external solution and 54 m Cl internal solution. This reversal potential shifted with changes in the transmembrane Cl gradient in the fashion expected for a chloride current. Anthracene-9-carboxylic acid and diphenylamine 2-carboxilic acid (chloride channels blockers) were found to be effective in blocking the AII-sensitive current. The linear segment of the current-voltage relation can be totally inhibited by the competitive AII-receptor (AT1) antagonist losartan and by the presence of intracellular protein kinase C inhibitor, whereas the outward rectification is only slightly changed. It is concluded that sino-atrial cells should contain protein-kinase-C-sensitive chloride channels which may be activated by angiotensin II via the stimulation of the AT1 receptors. [ABSTRACT FROM AUTHOR]

Voltage-clamp experiments were carried out in sheep Purkinje fibers in order to find an explanation for the prolongation of the action potential, the positive shift of the plateau, the hyperpolarization of the maximum diastolic potential and the increase in rate of diastolic depolarization, occurring in the presence of acetylcholine (Ach). In the presence of Ach the instantaneous current-voltage relation is shifted in the inward direction for potentials positive to −75 mV, while the opposite shift is obtained for more negative potentials; the results suggest a decrease in background conductance. The contribution of K, Cl, Na and Ca to the Ach sensitive current was studied by varying K concentration or adding 20 mmol·l Cs, by omitting Cl or Na, and by changing the Ca concentration. In 20 mmol·l Cs the apparent reversal potential of the Ach sensitive current is −50 mV, as compared to −75 mV in normal Tyrode. The component of the Ach sensitive current, which is suppressed by Cs, shows inward going rectification. In different K concentrations the reversal potential of the Ach sensitive current is changed; the shift obeys the theoretical change in equilibrium potential of K. The results are consistent with a decrease in K background current by Ach (inward and outward rectifier). In Cl free media the Ach sensitive current is not decreased excluding a major contribution of Cl ions. The Ach effect also persists in Na free media; the reversal potential of the Ach sensitive current is slightly shifted in the hyperpolarizing direction. These results indicate that active electrogenic pumps (Na or Na−Ca) do not play an important role; they are in accord with a reduction in inward Na background current by Ach. The shift of the current-voltage relation by Ach was greater the lower the Ca concentration; the mechanism is not clear. The inward shift of the current at −40 mV was dependent on the Ach concentration. Half-maximum effect was obtained at 3·10 mol·l Ach; the Hill coefficient was 1.12. It is concluded that Ach interacts in a one to one reaction with a muscarinic receptor and reduces the background current mainly carried by K (inward and outward rectifier), and less by Na (and probably Ca). [ABSTRACT FROM AUTHOR]

Submarine pipelines, as an important tool for oil and gas transportation, have been distributed in offshore oil and gas fields worldwide. Under extreme waves, a large number of submarine pipelines have been damaged in the past decades. In order to investigate the effect of extreme marine environments on the pipelines, the joint effect of solitary waves and background currents on the pipelines is numerically studied in this paper by using a numerical wave tank developed with a free surface tracking approach and the immersed boundary method. The sediment transport module including packed and suspended sediment is incorporated with the flow module. In order to ensure the calculation accuracy of this model, three verification cases related to the wave propagation profile, the hydrodynamic force on the cylinder and the scour hole profile are simulated and the numerical results match the experimental and analytical results well. Given the combined wave exerts on the different pipelines, the environmental variables consider the background current velocity and wave height, and the pipeline arrangement includes the different diameters and the suspended pipeline and tandem pipeline. It is noted that the hydrodynamic characteristics, the forces and the local scour around the pipeline are closely related to the background current and the diameter and layout of the pipeline. It is anticipated that the findings in this paper will enhance our understanding of the damage mechanism of submarine pipeline by waves and may also be useful in future design practices for pipelines. • A numerical wave tank is applied for the generation of combined wave of solitary wave and current. • The effects of the different combined waves on the submarine pipeline and the local scour are investigated. • The interaction between the sand bed and the different pipelines under the combined wave is studied. • The influence degree of background current and wave on the scour is obtained by comparing the scour hole profile. [ABSTRACT FROM AUTHOR]

Two-pore domain potassium channels are formed by subunits that each contain two pore-loops moieties. Whether the channels are expressed in yeast or the human central nervous system, two subunits come together to form a single potassium selective pore. TOK1, the first two-domain channel was cloned from Saccharomyces cerevisiae in 1995 and soon thereafter, 15 distinct K 2P subunits were identified in the human genome. The human K 2P channels are stratified into six K 2P subfamilies based on sequence as well as physiological or pharmacological similarities. Functional K 2P channels pass background (or "leak") K + currents that shape the membrane potential and excitability of cells in a broad range of tissues. In the years since they were first described, classical functional assays, latterly coupled with state-of-the-art structural and computational studies have revealed the mechanistic basis of K 2P channel gating in response to specific physicochemical or pharmacological stimuli. The growing appreciation that K 2P channels can play a pivotal role in the pathophysiology of a growing spectrum of diseases makes a compelling case for K 2P channels as targets for drug discovery. Here, we summarize recent advances in unraveling the structure, function, and pharmacology of the K 2 P channels., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)