Search

The Taranaki Basin, located offshore New Zealand, is a Cretaceous rift basin that has well defined yet complex Miocene deepwater sedimentary systems. We analyze a pronounced anomalous seismic response in a Late Miocene to Early Pliocene deepwater channel within the 2005 Hector 3D survey located in the southern Taranaki Basin. Several seismic attributes were calculated to interpret the extent of these anomalous features. Analogues within both the Iron River reservoir in Albania, Canada and the East Breaks Basin Four, offshore Gulf of Mexico suggest that these anomalous seismic features are most likely channel-body basal scours. Another interpretation suggests that these scours were formed and later filled by mass transport deposits (MTDs) with sediment ponding as suggested from some studies within the Molasse Basin in southern Germany. Alternatively, these scours could also be interpreted as pockmarks resulting from channel abandonment and fluid escape due to compaction. Others describe this process within submarine canyon systems, offshore Equatorial Guinea. However, there is compelling evidence to suggest that these features are most likely channel-body basal scours rather than being related to MTDs or pockmarks. Within all of the interpretations, there is evidence of differential compaction, which is further supported by the reflectors displaying a slight doming immediately above where the scours are located. Geological feature: Seismic geomorphology anomalies within a Pliocene deepwater channel complex in the Taranaki Basin, offshore New Zealand Seismic appearance: Asymmetric bowl-shaped geometry with high-amplitude reflectors that are incised into underlying sediment Alternative interpretations: Pockmarks resulting from channel abandonment and fluid escape due to compaction Features with similar appearance: Channel scours or pockmarks Formation: Mount Messenger Formation, Taranaki Basin Age: Late Miocene to Early Pliocene Location: Southern Taranaki Basin, New Zealand Available data: Hector 3D data set, Kiwa-1, and Hector-1 wells Analysis tools: 3D seismic data, well logs, and seismic attributes

We have constructed a channel complex model at a scale of 1:10,000 by stacking 3D-printed polylactide layers with negative relief meandering channels. This model was subjected to an ultrasonic common-offset acquisition in a water tank (with the water filling the channels), and the result was treated as a zero-offset 3D acoustic reflection seismogram, receiving a deterministic deconvolution and a poststack migration as data treatment. We then developed an algorithm to yield volumes of estimated two-way time layer thickness from multiple-frequency volumes obtained through the short-time Fourier transform. The estimated thicknesses were compared with the measurements of the physical model obtained through X-ray computed tomography. Despite the strong signal attenuation and imaging issues, the results were rather satisfactory, increasing the confidence in using spectral decomposition for quantitative seismic analysis.

Background: Ginsenoside Rk1, a saponin component isolated from heat-processed Panax ginseng Meyer, has been implicated in the regulation of antitumor and anti-inflammatory activities. Although our previous studies have demonstrated that ginsenoside Rg3 significantly attenuated the activation of NMDA receptors (NMDARs) in hippocampal neurons, the effects of ginsenosides Rg5 and Rk1, which are derived from heat-mediated dehydration of ginsenoside Rg3, on neuronal NMDARs have not yet been elucidated. Methods: We examined the regulation of NMDARs by ginsenosides Rg5 and Rk1 in cultured rat hippocampal neurons using fura-2–based calcium imaging and whole-cell patch-clamp recordings. Results: The results from our investigation showed that ginsenosides Rg3 and Rg5 inhibited NMDARs with similar potencies. However, ginsenoside Rk1 inhibited NMDARs most effectively among the five compounds (Rg3, Rg5, Rk1, Rg5/Rk1 mixture, and protopanaxadiol) tested in cultured hippocampal neurons. Its inhibition is independent of the NMDA- and glycine-binding sites, and its action seems to involve in an interaction with the polyamine-binding site of the NMDAR channel complex. Conclusion: Taken together, our results suggest that ginsenoside Rk1 might be a novel component contributable to the development of ginseng-based therapeutic treatments for neurodegenerative diseases. Keywords: Ginsenoside Rk1, Hippocampal neurons, Intracellular Ca2+, NMDA receptors, Whole-cell patch-clamp

In accordance with the water management zoning of the territory of Ukraine, the Poltva river basin belongs to the Vistula river basin region. The evaluation methodology of the channel and floodplain river complex state was proposed by Himko R. V. (2005). According to this methodology, the parameters (23 indicators), characterizing river state by points scale (5 quality classes), were defined. The research included three steps. During the preparatory stage cartographic materials were investigated and the coastal protection zones were highlighted. The fieldwork stage included: visual assessment of water quality and of the state of channels; identification of sources of pollution and clogging of waters and coastal areas; study of features of anthropogenic load within floodplains. In the third stage, generalization and evaluation works were carried out. Wastewater discharges from enterprises and coastal settlements affect the water quality of the study area. Lviv has the greatest economic impact on the Poltva river due to its channelling within the city and due to large volumes of wastewater discharges (121.4 million m3 in 2017). The water quality of the Poltva River tributaries depends on sewage discharges from small industrial and public utilities, as well as on unauthorized sewage discharges in villages. Significant parts of the river channels are regulated. Drainage systems, that occupy much of the study area, as well as ponds and small reservoirs, directly affect on the hydrological regime of the rivers. The level of land-use of coastal territories is characterized by their urbanization level and their level of plowing. The urbanization of the upper reaches of the Poltva river valley is a determining factor that has influenced the sanitary status of its channel. Outside the Lviv city, many coastal areas (within the coastal protection zones) are plowed. Overgrowing of waters and obstruction of channels by water and coastal plant remains lead to a significant deterioration of sanitary conditions of the rivers, hence to secondary contamination of its waters. Geoecological state of the Poltva river channel and floodplain complex was designated as «unsatisfactory» (4th grade from 5 classes), of Yarychivka and Gologirka river complexes – as «satisfactory» (3rd grade), of other rivers – as «rather good» (2nd grade). The rivers of the Poltva watershed are under significant economic influence. To improve the geoecological state of river channels and floodplains, a complex of water protection measures is required: reduction of insufficiently treated wastewater discharges of Lviv city; cleaning of watercourses; monitoring of compliance with water protection rules etc.

A new application of K-NN was implemented to classify various substances using measured UWB channel complex coefficients. This study provides a low-cost system to detect different substance...

Major reservoirs in Field A namely A-2, A-3U, A-3M, and A-3L, are deposited within a multi stacked channel complex system within Group I in Malay Basin. These reservoirs were previously understood based on existing data to have no or very minimal vertical communication between them and are treated as separate systems. In 2018, three wells were proposed to drain the attic oil in the north region of A-3U reservoir. When drilling these infill wells, it was discovered that the pressure has exceeded initial reservoir pressure although the reservoir has been idle for almost a year prior to the drilling. The results of the multi-rate test of two of the three infill wells that are less than 1 km apart are significantly different from one another. Post drilling, more tests were executed to investigate the connection between the sand. Studies were also done by incorporating the static and dynamic reservoir modeling data. Based on the result of the tests and studies, it was concluded that all of the major sands are connected at some areas. This new finding on the connectivity might be able to explain the additional volume needed to history match some of the reservoirs. Establishing stratigraphy concepts of a reservoir particularly in a channel complex system is an ongoing process, in this case, a brown field of almost 20 years of production. All data including new well data and dynamic data plays a vital role for a better understanding of the reservoir. It is essential to incorporate the updated geological understanding into the static model to have a representative simulation for better history matching and prediction. Moving forward, instead of building a separate grid model for each reservoir, a larger framework consist of intercalated reservoir grids will be built with this new geological understanding for dynamic simulation.

The article presents a comprehensive assessment of the geoecological risk of the Belaya River floodplain (Republic of Bashkortostan, Russia). The risk assessment of the floodplain-channel complex includes the risk of depletion by the plant species composition and the risk of depletion of the ecological and hydrological states. Geographic information maps of the floodplain were compiled for vegetation and floodplain forests and wetlands. The extent of forest cover was chosen as an indicator of the floodplain’s resilience to the risk of depletion and decline. The calculation of the risk of depletion of floodplains based on the ecological and hydrological state was carried out taking into account the changes in floodplain areas over the past 10 years, data on the catchment of ground and surface waters, “sealed” areas and the annual average discharge. The assessment and zoning of the river floodplain territory was carried out according to the proposed method.

A reversible pseudo-single-ligand-gated ion transportation switch of ON–OFF–ON type was achieved through host–guest complexation with pillar[6]arene (P[6]) as the ion channel, and a photoresponsive azobenzene as the dual-role (open and close) ligand.

Resting membrane potential determines the excitability of the cell and is essential for the cellular electrical activities. The NALCN channel mediates sodium leak currents, which positively adjust resting membrane potential towards depolarization. The NALCN channel is involved in several neurological processes and has been implicated in a spectrum of neurodevelopmental diseases. Here, we report the cryo-EM structure of rat NALCN and mouse FAM155A complex to 2.7 Å resolution. The structure reveals detailed interactions between NALCN and the extracellular cysteine-rich domain of FAM155A. We find that the non-canonical architecture of NALCN selectivity filter dictates its sodium selectivity and calcium block, and that the asymmetric arrangement of two functional voltage sensors confers the modulation by membrane potential. Moreover, mutations associated with human diseases map to the domain-domain interfaces or the pore domain of NALCN, intuitively suggesting their pathological mechanisms., The NALCN channel mediates sodium leak currents, which in turn adjusts resting membrane potential and neuronal excitability. Here the authors describe a cryo-EM structure of mammalian NALCN-FAM155A channel complex, showing how selectivity filter contributes to sodium permeation and calcium block and how the voltage sensors contribute to current modulation.

The voltage-gated potassium channel Kv1.2 plays a pivotal role in neuronal excitability and is regulated by a variety of known and unknown extrinsic factors. The canonical accessory subunit of Kv1.2, Kvβ, promotes N-type inactivation and cell surface expression of the channel. We recently reported that a neutral amino acid transporter, Slc7a5, alters the function and expression of Kv1.2. In the current study, we investigated the effects of Slc7a5 on Kv1.2 in the presence of Kvβ1.2 subunits. We observed that Slc7a5-induced suppression of Kv1.2 current and protein expression was attenuated with cotransfection of Kvβ1.2. However, gating effects mediated by Slc7a5, including disinhibition and a hyperpolarizing shift in channel activation, were observed together with Kvβ-mediated inactivation, indicating convergent regulation of Kv1.2 by both regulatory proteins. Slc7a5 influenced several properties of Kvβ-induced inactivation of Kv1.2, including accelerated inactivation, a hyperpolarizing shift and greater extent of steady-state inactivation, and delayed recovery from inactivation. These modified inactivation properties were also apparent in altered deactivation of the Kv1.2/Kvβ/Slc7a5 channel complex. Taken together, these findings illustrate a functional interaction arising from simultaneous regulation of Kv1.2 by Kvβ and Slc7a5, leading to powerful effects on Kv1.2 expression, gating, and overall channel function.

NALCN is the voltage-sensing, pore-forming subunit of a constitutively active, extracellular calcium-regulated complex., The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80, and FAM155A. The resulting NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca2+. Despite the smaller number of voltage-sensing residues in NALCN, the constitutive activity is modulated by voltage, suggesting that voltage-sensing domains can give rise to a broader range of gating phenotypes than previously anticipated. Our work points toward formerly unknown contributions of NALCN to neuronal excitability and opens avenues for pharmacological targeting.

Chlordane is a worldwide banned organochlorine insecticide because of its hazard to animal and human health. It is also a persistent organic pollutant, which can affect either the soil or the aquatic life. The same applies to other chlorinated cyclodiene insecticides, such as dieldrin and aldrin. In turn, organofluorine compounds have a widespread use in agriculture. Therefore, density functional calculations and docking studies showed that the bioisosteric replacement of chlorines in the above-mentioned compounds by fluorines improves some physicochemical parameters used to estimate the toxicity and environmental risk of these compounds, as well as the ligand-enzyme (GABAA receptor-chloride channel complex) interactions related to their insecticidal activity. This work is an effort to provide an improved new class of organofluorine pesticides.

The turbidite is favorable for accumulation of oil and gas and it is the most important reservoir in the deepwater area of West Africa. Currently, some commercial discoveries in such the deepwater area generally belong to turbidite sandstone reservoirs. Based on comprehensive analysis of lithology, lithofacies and configuration of the turbidite, and combined with changes of seismic attributes and sedimentary cycle, the turbidite in the deepwater area of West Africa can be classified into by-pass channel (including the constructive by-pass channel and the erosive by-pass channel), confined channel complex, weakly confined channel complex, and lobe. Different types of turbidite reservoirs have different physical property, so there are differences in hydrocarbon exploration potential; the sandstone in the weakly confined channel complex is the key exploration target in the deepwater area of the Angola Sea. Keywords: Turbidite, Channel, Sandstone, Reservoir architecture, Seismic attributes, Lower Congo Basin, West Africa

Ion channels control the membrane potential and mediate transport of ions across membranes. Archetypical physiological functions of ion channels include processes such as regulation of neuronal excitability, muscle contraction, or transepithelial ion transport. In that regard, transient receptor potential ion channel polycystin 2 (TRPP2) is remarkable, because it controls complex morphogenetic processes such as the establishment of properly shaped epithelial tubules and left-right-asymmetry of organs. The fascinating question of how an ion channel regulates morphogenesis has since captivated the attention of scientists in different disciplines. Four loosely connected key insights on different levels of biological complexity ranging from protein to whole organism have framed our understanding of TRPP2 physiology: 1) TRPP2 is a non-selective cation channel; 2) TRPP2 is part of a receptor-ion channel complex; 3) TRPP2 localizes to primary cilia; and 4) TRPP2 is required for organ morphogenesis. In this review, we will discuss the current knowledge in these key areas and highlight some of the challenges ahead.

SummaryThe sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that the robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80 and FAM155A. The resulting NALCN channel complex is constitutively active, conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca2+. Despite the smaller number of voltage-sensing residues in the putative voltage sensors of NALCN, the channel complex shows voltage-dependent modulation of the constitutive current, suggesting that voltage-sensing domains can give rise to a broader range of gating phenotypes than previously anticipated. Our work points towards formerly unknown contributions of NALCN to neuronal excitability and opens avenues for pharmacological targeting.HighlightsFunction of NALCN requires UNC79, UNC80 and FAM155AThe complex is permeable to monovalent cations, but is blocked by divalent cationsThe complex displays a constitutively active, voltage-modulated current phenotypePositively charged side chains in S4 of NALCN VSD I and II confer voltage sensitivity

Protein translocating Cag type IV secretion system of Helicobacter pylori is a diverse multi-protein complex. Here, we have characterized one of its key subunit CagW to identify its interacting partners. Our results demonstrate for the first time that this VirB6 homologue interacts with the substrate of the secretion system CagA. CagW forms multimer and its absence affects cellular levels of pilus forming components, CagL, CagI and CagH. Our results support the notion that the protein is essential for the transport of CagA across the bacterial membrane barrier and would aid in improving our understanding of structural and functional aspects of the inner membrane part of Cag-T4SS channel complex for the passage of substrate CagA.

The Bengal Fan has attracted extensive attention from the oil industry because of its hydrocarbon reservoir potential. This paper characterizes the architectural elements and stratigraphy of the Upper Miocene-Pliocene Bengal Fan by high-resolution 3D seismic data. Seismic facies and strata slice technologies are applied to identify architectural elements. Six seismic facies are classified and interpreted as mass-transport deposits, channel complex including incised channel, leveed channel and sinuous channel, lobe complex, and hemipelagic deposits. Two seismic sequences and five internal sequences are divided according to the vertical evolution of deepwater sedimentary elements. By understanding and identifying the architectural elements and stratigraphy of the deepwater fan, we can propose potential drilling sequences of oil and gas reservoirs.

In northeastern Montana, fossil localities in the Garbani Channel Complex and other early Paleocene (Puercan 3 Interval Zone) localities are preserved in the Tullock Member of the Fort Union Formation. They document an early phase in the recovery of the terrestrial fauna of the North American Western Interior after the mass extinction marking the Cretaceous-Paleogene (K-Pg) boundary. The cimolestids Puercolestes simpsoni and Betonnia tsosia were typified on fragmentary jaws and isolated teeth found in Puercan 2 and 3 Interval Zones (Pu2, Pu3) in the Nacimiento Formation, San Juan Basin, New Mexico. The available samples of these genera from both New Mexico and Montana are small and dominantly consist of isolated teeth. Characters of upper cheek teeth, P4 and M1–M3, justify provisional recognition of Puercolestes sp. cf. Pu. simpsoni and the somewhat smaller Betonnia sp. cf. Be. tsosia in Pu3 local faunas in the Tullock Member. In contrast, discovery of characters distinguishing the isolated lower cheek teeth, p4s and m1–m3s, of these species must await recovery of dentulous dentaries documenting the patterns of morphological variation of their lower dentitions. Fossils from the Tullock Member add support to the current interpretation that cimolestids were taxonomically diverse and geographically widespread but relatively rare members of the faunas of the North American Western Interior during approximately the first million years of the Paleocene.

"This prediction demonstrates an inclusive investigation on" single-phase and two- phase pressure drop properties and flows boiling" instabilities in micro-channels to resume the concepts in the boiling heat transfer tests". The predictions of "single-phase and two- phase heat transfers" in the aluminum micro-channel heat sink have been investigated". "Different heat fluxes and different mass fluxes have been applied "(each mass flow rate under numerous heats fluxes) in an aluminum parallel channel test piece is tested". "It was built up from a piece of aluminum," twenty-five mm wide by twenty-five mm long and ten mm high"."R113 working fluid temperature was constant (25°C) for all prediction tests; "Therefore the heat applies have been applied "in the ranges of (40-600 Watts) "The processes and iteration loops have reached for the prediction heat transfer properties "for three mass flow rates are (0.0125;0.015 and 0.0175 kg/s) "respectively;" and another heat transfer properties. "The aluminum micro-channels heat sink" with 0.5 mm channel height and 0.5 mm channel width "is heated via a wire electrical heater device". "The single-phase and two-phase flows are important parameters" for geometrical configuration of the aluminum micro-channels under variations heat applied". The purpose of this investigation is to explore the relationship between "prediction heat transfer coefficients and mini-scale heat sink geometrical configuration". Heat-transfer coefficients and pressure drops are investigated"." For sub-cooled and saturated boiling data acquired with Single-phase and boiling flows," The single-phase consequences are seen to be location-following, regular with a fully developed laminar flow. All the prediction boiling heat transfer coefficients are seen to have reasonably relied on as mass fraction and mass flux"."" Nevertheless, some are seen to have relied on heat flux whereas others are not. The convective boiling consisting is seen to have a boiling heat-transfer coefficient that is moderately relied on mass flow rate, gas mass fraction, and heat applied"." The prediction work presented here provides one of the first investigations into how to get single-phase" and two-phase properties" data via computer programming. In the end, "the single-phase and two-phase" heat transfer coefficients are reported" for square aluminum micro-channels heat sink under" boiling tests".

Auxiliary α2δ subunits are important proteins for trafficking of voltage-gated calcium channels (CaV) at the active zones of synapses. We have previously shown that the post-translational proteolytic cleavage of α2δ is essential for their modulatory effects on the trafficking of N-type (CaV2.2) calcium channels (Kadurin et al., 2016). We extend these results here by showing that the probability of presynaptic vesicular release is reduced when an uncleaved α2δ is expressed in rat neurons and that this inhibitory effect is reversed when cleavage of α2δ is restored. We also show that asynchronous release is influenced by the maturation of α2δ−1, highlighting the role of CaV channels in this component of vesicular release. We present additional evidence that CaV2.2 co-immunoprecipitates preferentially with cleaved wild-type α2δ. Our data indicate that the proteolytic maturation increases the association of α2δ−1 with CaV channel complex and is essential for its function on synaptic release.

Organochlorine pesticides have been extensively used in the past, but due to both their environmental persistence and neurotoxicity their use has been banned or greatly reduced in the last decades. Pyrethroids are among the most used insecticides. The main effects of both organochlorines and pyrethroids are on the nervous system by interference with different ion channels; DDT and analogs, and pyrethroids interfere mainly sodium channels causing both central and peripheral nervous effects; lindane and cyclodienes mainly the gamma-aminobutyric acid (GABA) A -receptor–chloride channel complex. In addition, developmental neurotoxic effects have been demonstrated in animals perinatally exposed to either DDT and analogs or pyrethroids. Data in humans do not show convincing evidence of such effects. Also some epidemiological studies indicate a relation between parkinsonism and exposure to organochlorines or pyrethroids, but experimental data do not strongly support a causative role of these compounds.

Mechanotransduction, the conversion of mechanical forces into biological signals, plays critical roles in various physiological and pathophysiological processes in mammals, such as conscious sensing of touch, pain, and sound, as well as unconscious sensing of blood flow-associated shear stress, urine flow, and bladder distention. Among the various molecules involved in mechanotransduction, mechanosensitive (MS) cation channels have long been postulated to represent one critical class of mechanotransducers that directly and rapidly converts mechanical force into electrochemical signals. Despite the awareness of their functional significance, the molecular identities of MS cation channels in mammals had remained elusive for decades till the groundbreaking finding that the Piezo family of genes, including Piezo1 and Piezo2, constitutes their essential components. Since their identification about 6 years ago, tremendous progress has been made in understanding their physiological and pathophysiological importance in mechanotransduction and their structure–function relationships of being the prototypic class of mammalian MS cation channels. On the one hand, Piezo proteins have been demonstrated to serve as physiologically and pathophysiologically important mechanotransducers for most, if not all, mechanotransduction processes. On the other hand, they have been shown to form a remarkable three-bladed, propeller-shaped homotrimeric channel complex comprising a separable ion-conducting pore module and mechanotransduction modules. In this chapter, we review the major advancements, with a particular focus on the structural and biophysical features that enable Piezo proteins to serve as sophisticated MS cation channels for force sensing, transduction, and ion conduction.

The excited hyperon Λ ( 1405 ) is the important building block for kaonic nuclei which are a nuclear many-body system with anti-kaons. We have been investigating the Λ ( 1405 ) resonance with the coupled-channel Complex Scaling Method (ccCSM) in which the Λ ( 1405 ) is treated as a hadron-molecular state of a K ¯ N – πΣ coupled system. We use a K ¯ N (– πY ) potential based on the chiral SU(3) theory. In this article, we report the double-pole nature of the Λ ( 1405 ) , which is a characteristic property predicted by many studies with chiral SU(3)-based models. With the help of the complex-range Gaussian basis in ccCSM, we have found successfully another pole besides a pole near the K ¯ N threshold (called higher pole) which was found in our previous work with the real-range Gaussian basis. The new pole (called lower pole) is found far below K ¯ N threshold: ( M , − Γ / 2 ) = ( 1395 , − 138 ) MeV when f π = 110 MeV . In spite of so broad width of the lower-pole state, the state is clearly identified with good separation from continuum states, since the oscillatory behavior of the continuum states is improved owing to the complex-range Gaussian basis. Analyzing the ccCSM wave function of the lower pole, we have revealed explicitly that the lower-pole state is dominated by the πΣ component rather than the K ¯ N component. We have confirmed that the ccCSM wave function is correctly connected to the asymptotic form of the resonance wave function. Estimating the meson–baryon mean distance for the lower-pole state which involves a large decay width, the obtained value has a large imaginary part comparable to a real part. Therefore, the mean-distance of the lower-pole state is difficult to be interpreted intuitively. Such a nature of the lower pole is different from that of the higher pole. In addition, we have investigated the origin of the appearance of the lower pole. The lower pole is confirmed to be generated by the energy dependence attributed to the chiral dynamics, by comparing the result of an energy-independent potential.

K+ channels containing Kv4.2 and Kv4.3 pore-forming subunits mediate most of the subthreshold-operating somatodendritic A-type K+ current in CNS neurons. These channels are believed to be important in regulating the frequency of repetitive firing, the backpropagation of action potential into dendrites, and dendritic integration and plasticity. Moreover, they have been implicated in several diseases from pain to epilepsy and autism spectrum disorders. The lack of toxins that specifically and efficiently block these channels has hampered studies aimed at confirming their functional role and their involvement in disease. AmmTX3 and other related members of the α-KTX15 family of scorpion toxins have been shown to block the A-type K+ current in cultured neurons, but their specificity has been questioned because the toxins do not efficiently block the currents mediated by Kv4.2 or Kv4.3 subunits expressed in heterologous cells. Here we show that the high-affinity blockade of Kv4.2 and Kv4.3 channels by AmmTX3 depends on the presence of the auxiliary subunits DPP6 and DPP10. These proteins are thought to be components of the Kv4 channel complex in neurons and to be important for channel expression in dendrites. These studies validate the use of AmmTX3 as a blocker of the Kv4-mediated A-type K+ current in neurons.

This Focus Issue highlights research into cell-specific regulation of store-operated calcium entry through the ORAI/STIM channel complex. Understanding the properties of these channels and how ORAI activity is regulated will lead to a better molecular view of immune cell function and diseases involving the immune system.

Calmodulin (CaM), a bi-partite protein, binding to the A-B module, a bi-partite target, affect the function of Kv7.2 subunits, which are the main component of the non-inactivating K+ M-current, a key controller of neuronal excitability. Simultaneous binding to helix A and B is crucial for trafficking to the plasma membrane, and mediates Ca2+-dependent inhibition of channel function. We have resolved the [CaM]/[AB-Kv7.2] complex by NMR and characterized the influence of Ca2+ on the structure. The results suggest a reorientation of A-B helices triggered by Ca2+. How this structural change may propagate to affect gating will be discussed.