Anion Permeability Research Articles

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR): CLOSED AND OPEN STATE CHANNEL MODELS

The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporter superfamily. CFTR controls the flow of anions through the apical membrane of epithelia. Dysfunctional CFTR causes the common lethal genetic disease cystic fibrosis. Transitions between open and closed states of CFTR are regulated by ATP binding and hydrolysis on the cytosolic nucleotide binding domains, which are coupled with the transmembrane (TM) domains forming the pathway for anion permeation. Lack of structural data hampers a global understanding of CFTR and thus the development of "rational" approaches directly targeting defective CFTR. In this work, we explored possible conformational states of the CFTR gating cycle by means of homology modeling. As templates, we used structures of homologous ABC transporters, namely TM(287-288), ABC-B10, McjD, and Sav1866. In the light of published experimental results, structural analysis of the transmembrane cavity suggests that the TM(287-288)-based CFTR model could correspond to a commonly occupied closed state, whereas the McjD-based model could represent an open state. The models capture the important role played by Phe-337 as a filter/gating residue and provide structural information on the conformational transition from closed to open channel.

Ion-Responsive Channels of Zwitterion-Carbon Nanotube Membrane for Rapid Water Permeation and Ultrahigh Mono-/Multivalent Ion Selectivity

The rational combination of polymer matrix and nanostructured building blocks leads to the formation of composite membranes with unexpected capability of selectivity of monovalent electrolytes and water, which affords the feasibility to effeciently remove harmful ions and neutral molecules from the environment of concentrated salines. However, the multivalent ion rejection in salined water of routine nanocomposite membranes was less than 98% when ion strength is high, resulting in a poor ion selectivity far below the acceptable value. In this contribution, the ion-responsive membrane with zwitterion-carbon nanotube (ZCNT) entrances at the surface and nanochannels inside membrane has been proposed to obtain ultrahigh multivalent ion rejection. The mean effective pore diameter of ZCNT membrane was dedicated tuned from 1.24 to 0.54 nm with the rise in Na2SO4 concentration from 0 to 70 mol m(-3) as contrary to the conventional rejection drop in carbon nanotube (CNT) membrane. The ultrahigh selective permeabilities of monovalent anions against divalent anions of 93 and against glucose of 5.5 were obtained on ZCNT membrane, while such selectivities were only 20 and 1.6 for the pristine CNT membrane, respectively. The ZCNT membranes have potential applications in treatment of salined water with general NaCl concentration from 100 to 600 mol m(-3), which are widely applicable in desalination, food, and biological separation processes.

PH Sensitivity of Ion Exchange through a Thin Film Composite Membrane in Forward Osmosis

The uneven permeation of cations and anions through forward osmosis membranes offers a new technical challenge in the development of forward osmosis processes. Cation exchange in polyamide thin film composite membranes is caused by carboxylic acid functional groups within the structure of these membranes’ selective layers. These functional groups will gain or lose a proton depending on the external solution pH. The deprotonation of a polyamide at alkaline pHs results in a net negative charge, allowing for the exchange of cations between feed and draw solutions having monovalent cations. In this study, the importance of solution pH in influencing cation transport across a commercial thin film composite forward osmosis membrane was examined. It was found that cation transport across this membrane varies significantly with changes in pH and occurred fastest at alkaline pH.

Rol de las claudinas en el manejo renal del calcio

Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH) is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR), which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline.

Role of claudins in renal calcium handling

Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH) is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR), which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline.

Molecular Mechanisms That Underlie The [Cl-]I-Sensitive Kinases-Mediated Regulation of Cftr Anion Selectivity

MoleculAr MechAnisMs ThAT underlie The [cl-]i-sensiTive KinAses-MediATed regulATion of cfTr Anion selecTiviTy I. Jun; J. Jang; J. Jung; Y. Kim; and M.G. Lee Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea; and Department of Hematology, Yonsei University College of Medicine, Seoul 120-752, Korea Introduction: CFTR is cAMP activated anion channel which secretes chloride and bicarbonate in airway, exocrine pancreas, intestine, and genitourinary systems. Human pancreas secretes pancreatic juice which contains as much as 140 mM bicarbonate (HCO3-) via CFTR. Recently, we have shown that [Cl-]i-sensitive activation of WNK1OSR1/SPAK pathway plays a critical role in pancreatic HCO3secretion by increasing the bicarbonate permeability (PHCO3/PCl) of CFTR. However, how [Cl-]i-sensitive kinases modulate PHCO3/ PCl of CFTR remains elusive. Material and Methods: Overexpression and knockdown of each kinase in HEK293T cells were performed. Using patch clamp, we measured permeability of bicarbonate and halide ions. We did pulldown assay between truncated WNK1 and CFTR at 150mM and 0mM Clconcentrations. Results: WNK1 affects permeability of other anions as well as bicarbonate in patch clamp recordings. Especially, the interval of relative permeabilities (Px/PCl) between each anion was greatly narrowed by WNK1. Consequently, WNK1 increased the dielectric constant of the hypothetical selectivity filter of CFTR. And we measured the pore size of CFTR at each state. WNK1 makes CFTR pore size larger. We figured out that WNK1 kinase domain binds to CFTR and truncated forms of WNK1 respond to low Clconcentrations. Conclusions: These findings suggest that WNK1 increases the bicarbonate permeability of CFTR by modulating the polarizability of anion selectivity filter and provide insight into the fundamental question of how ion selectivity of anion channels can be regulated by cytosolic signaling at the molecular level. Furthermore, WNK1 senses low [Cl-]i, then kinase domain is exposed and binds to CFTR.

The Fifth Transmembrane Segment of Cystic Fibrosis Transmembrane Conductance Regulator Contributes to Its Anion Permeation Pathway.

Previous studies have identified several transmembrane segments (TMs), including TM1, TM3, TM6, TM9, TM11, and TM12, as pore-lining segments in cystic fibrosis transmembrane conductance regulator (CFTR), but the role of TM5 in pore construction remains controversial. In this study, we employed substituted cysteine accessibility methodology (SCAM) to screen the entire TM5 defined by the original topology model and its cytoplasmic extension in a Cysless background. We found six positions (A299, R303, N306, S307, F310, and F311) where engineered cysteines react to intracellular 2-sulfonatoethyl methanethiosulfonate (MTSES⁻). Quantification of the modification rate of engineered cysteines in the presence or absence of ATP suggests that these six residues are accessible in both the open and closed states. Whole-cell experiments with external MTSES⁻ identified only two positive positions (L323 and A326), resulting in a segment containing 11 consecutive amino acids, where substituted cysteines respond to neither internal nor external MTSES⁻, a unique feature not seen previously in CFTR's pore-lining segments. The observation that these positions are inaccessible to channel-permeant thiol-specific reagent [Au(CN)₂]⁻ suggests that this segment of TM5 between F311 and L323 is concealed from the pore by other TMs and/or lipid bilayers. In addition, our data support the idea that the positively charged arginine at position 303 poses a pure electrostatic action in determining the single-channel current amplitude of CFTR and the effect of an open-channel blocker glibencalmide. Collectively, we conclude that the cytoplasmic portion of CFTR's TM5 lines the pore. Our functional data are remarkably consistent with predicted structural arrangements of TM5 in some homology models of CFTR.

Facile preparation of 1,8-Diazabicyclo[5.4.0]undec-7-ene based high performance anion exchange membranes for diffusion dialysis applications

Anion exchange membranes (AEMs) based on new ion exchanging groups were successfully prepared by functionalization of brominated poly(2,6-dimethyl-1,4-phenylene oxide) with 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU). High anion permeability was observed due to good self-dissociation ability of anion exchanging groups-anion ion pairs attributing to high basicity of DBU. When used in diffusion dialysis (DD) for acid recovery from a simulated iron polishing waste solution (HCl, 1.27mol/L; FeCl2, 0.20mol/L), the as-prepared membranes exhibit extraordinary proton diffusion coefficient (U) of 0.027m/h and high separation factor of 62.6 at 30°C, implying the synthesized AEM is a prospective candidate to be applied in the field of acid recovery.

Study of permeation and blocker binding in TMEM16A calcium-activated chloride channels

We studied the effects of mutations of positively charged amino acid residues in the pore of X. tropicalis TMEM16A calcium-activated chloride channels: K613E, K628E, K630E; R646E and R761E. The activation and deactivation kinetics were not affected, and only K613E showed a lower current density. K628E and R761E affect anion selectivity without affecting Na+ permeation, whereas K613E, R646E and the double mutant K613E + R646E affect anion selectivity and permeability to Na+. Furthermore, altered blockade by the chloride channel blockers anthracene-9-carboxylic acid (A-9-C), 4, 4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) and T16inh-A01 was observed. These results suggest the existence of 2 binding sites for anions within the pore at electrical distances of 0.3 and 0.5. These sites are also relevant for anion permeation and blockade.

Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels

TMEM16A (transmembrane protein 16) (Anoctamin-1) forms a calcium-activated chloride channel (CaCC) that regulates a broad array of physiological properties in response to changes in intracellular calcium concentration. Although known to conduct anions according to the Eisenman type I selectivity sequence, the structural determinants of TMEM16A anion selectivity are not well-understood. Reasoning that the positive charges on basic residues are likely contributors to anion selectivity, we performed whole-cell recordings of mutants with alanine substitution for basic residues within the putative pore region and identified four residues on four different putative transmembrane segments that significantly increased the permeability of the larger halides and thiocyanate relative to that of chloride. Because TMEM16A permeation properties are known to shift with changes in intracellular calcium concentration, we further examined the calcium dependence of anion selectivity. We found that WT TMEM16A but not mutants with alanine substitution at those four basic residues exhibited a clear decline in the preference for larger anions as intracellular calcium was increased. Having implicated these residues as contributing to the TMEM16A pore, we scrutinized candidate small molecules from a high-throughput CaCC inhibitor screen to identify two compounds that act as pore blockers. Mutations of those four putative pore-lining basic residues significantly altered the IC50 of these compounds at positive voltages. These findings contribute to our understanding regarding anion permeation of TMEM16A CaCC and provide valuable pharmacological tools to probe the channel pore.

Location of a permeant anion binding site in the cystic fibrosis transmembrane conductance regulator chloride channel pore.

In the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, lyotropic anions with high permeability also bind relatively tightly within the pore. However, the location of permeant anion binding sites, as well as their relationship to anion permeability, is not known. We have identified lysine residue K95 as a key determinant of permeant anion binding in the CFTR pore. Lyotropic anion binding affinity is related to the number of positively charged amino acids located in the inner vestibule of the pore. However, mutations that change the number of positive charges in this pore region have minimal effects on anion permeability. In contrast, a mutation at the narrow pore region alters permeability with minimal effects on anion binding. Our results suggest that a localized permeant anion binding site exists in the pore; however, anion binding to this site has little influence over anion permeability. Implications of this work for the mechanisms of anion recognition and permeability in CFTR are discussed.

Potentiation of CFTR Gating by an Energetically Additive Mechanism

CFTR is the only member of the ATP-binding cassette (ABC) protein superfamily that functions as an ion channel. Once its regulatory (R) domain is phosphorylated, CFTR will harness the free energy from ATP binding/hydrolysis in the nucleotide-binding domains (NBDs) to power the conformational changes of the gate located in the transmembrane domains (TMDs). We inadvertently found that some permeant anions such as nitrate or bromide, when applied to the cytoplasmic side of the channel, can increase the Po of CFTR by raising slightly the opening rate but decreasing considerably the closing rate. Since nitrate also decelerates non-hydrolytic closing, we conclude that the effect of nitrate is independent of ATP hydrolysis. Surprisingly, despite their markedly different physical properties, the gating effects of nitrate are remarkably similar to those of VX-770, a well-characterized CFTR potentiator now used in clinics. Nonetheless, while VX-770 is equally effective when applied from either side of the membrane, nitrate potentiates gating mainly from the cytoplasmic side, implicating a common mechanism for gating modulation but via two distinct sites of action. Since nitrate increases the Po of ΔR- as well as ΔNBD2-CFTR, we exclude the R domain and NBD dimer as potential targets for nitrate. Furthermore, for both G551D- and ΔNBD2-CFTR, two mutants with extremely low Po, we show that the fold-increase of the Po by nitrate plus VX-770 is virtually the same as the product of fold increases by individual reagents. Collectively, our data suggest that nitrate and VX-770 independently affect CFTR gating by shifting the equilibrium of gating conformational changes of the TMDs towards the open channel configuration. These results may not only shed light on the future development of novel therapeutical reagents, but also provide insights into the coupling mechanism of gate opening/closing and NBD dimerization/dissociation.

Can ClC-2 Chloride Channel be Activated by Hyperpolarization Alone in Cells Dialyzed with Non-Permeant Anions?

Open and closing of ion channels is driven by conformational changes triggered by either an intrinsic voltage sensor in voltage-gated channels or by ligand binding in ligand-gated channels. However, ClC-2, a two pore Cl− channel is activated by hyperpolarisations despite of lacking of an intrinsic voltage sensor. The structural information available to date strongly suggests that in the closed conformation each pore of ClC-2 is occluded by the negatively charged side chain of a glutamate residue. Although the gating mechanism is unknown, there is evidence which indicates that intracellular anions and extracellular protons regulate gating. The present work was aimed to determine the contribution of pore occupancy caused by intracellular anions in gating the mouse ClC-2 channel. In our experiments, ClC-2 was readily activated by hyperpolarisations when permeant anions such Cl−, SCN−, Br− and I− were present on either side of the membrane. However, ClC-2 was not activated in cells dialyzed with acetate (0 Cl−) and exposed to [H+]O=10−7.3 M. In contrast, the channels were opened by increasing [Cl−]i at [H+]O=10−10 M_a condition unlikely to protonate the glutamate's side chain. Importantly, voltage gating occurred when F− or glutamate were present in the cytosolic side. Since these two anions are non-permeant we propose that they must enter the pore and interact with the glutamate side chain from the inside in order to induce opening. Thus, we propose that a strong hyperpolarisation drives the intracellular anions into the permeation pathway and the subsequent electrostatic interaction between the anions and the negatively charged side chain opens the pore. Our data support the hypothesis that voltage-dependent gating in mouse ClC-2 requires intracellular anions. Supported by grant 219949 from CONACyT.

Extracellular Chloride Regulates TMEM16A Gating

The gating mechanism of TMEM16A, an essential subunit of the Ca2+-activated Cl- channel, remains incompletely understood. Gating of TMEM16A channels is complex because elevation of intracellular calcium concentration ([Ca2+]i), strong depolarizations (Vm), and high extracellular Cl or highly permeant anions seem to contribute. In the present work we show that in TMEM16A no gating currents can be detected, however, external Cl ions might play a role in voltage sensing because the kinetics and magnitude of current activation were dependent on [Cl-]e. The onset and offset of Cl- currents produced by 0.5 s depolarisations of cells bathed in 137 mM [Cl-]e followed a mono-exponential behaviour; a subsequent reduction of [Cl-]e to 10 mM diminished the conductance ∼2-fold. These data suggest a single gating process regulated by extracellular Cl-. In contrast, when cells were exposed to 137 mM [Cl-]e the onset and offset currents elicited by 20s depolarisations exhibited fast and slow kinetics. Activation of the slow component resulted in large onset Cl- currents that did not reach steady-state at the end of the 20s pulse. This behaviour was abolished after activating TMEM16A with 5 µM [Ca2+]i or after deleting four residues (448EAVK451) located in the first intracellular loop. Deleting four additional residues (444EEEEEAVK451) resulted in Cl- currents that decayed at the end of the 20 s depolarization. To explain our data we developed a 12-state gating model assuming that TMEM16A is activated by a direct, Vm-dependent binding of two Ca2+ ions. In this model external Cl- increases channel open probability by promoting stable Vm-dependent Ca2+ binding. Our model reproduced the gating behaviour of the TMEM16A currents in response to voltage, Ca2+, and [Cl-]e. Thus, we conclude that external Cl stabilises Ca binding and promotes two gating modes in TMEM16A. Supported by grant 219949 from CONACyT.

Purified human brain calmodulin does not alter the bicarbonate permeability of the ANO1/TMEM16A channel

[Jung and Lee][1] have responded in this issue to our recent paper ([Yu et al., 2014b][2]) in which we concluded that calmodulin (CaM) does not alter anion permeability of the mouse ANO1/TMEM16A Ca2+-activated Cl− channel. In our paper, we suspected that the Ca2+-CaM (abbreviated as CaM) effect

Electricity generation and local ion ordering induced by cation-controlled selective anion transportation through graphene oxide membranes

A cation-controlled selective anion transportation through graphene oxide (GO) membranes is demonstrated in this work. The results reveal that the trans-membrane transport of different anions can be modulated by the corresponding cations. The diverse interactions among anions, cations, and the negatively charged GO membranes are responsible for selective anion permeation through GO membranes. During the ion penetration, electrical potential differences can be generated across drain and source as well as across GO membranes; based on this, the ion distributions around GO membranes can be determined. The results indicate that local ion ordering can be achieved by GO membranes. Interestingly, for the cases of KNO3, Ca(NO3)2, and Ba(NO3)2, alternate aggregations of metallic cations and NO3− anions can be formed around GO membranes, demonstrating the fantastic ability of these membranes for ordering the ions locally in solutions. In addition, based on the electrical potential differences generated by different salts, chlorides are demonstrated to be ideal sources for efficient practical electricity production compared to sulfates and nitrates, while the different voltage signals generated can be used to identify different source solutions for liquid sensing applications. These results indicate that GO membranes can find potential applications in membrane separation, energy generation, ion recognition, and local ion organizing.

In vitro action of 2.2’-azobis-2 amidinopropan dihydrochloride,red wine polyphenols, resveratrol and catechin on anion permeability for chloride in human red blood cell

Introduction: The purpose of this study was to evaluate the ability of polyphenols (red wine polyphenols, resveratrol and catechin) on anion permeability for chloride and oxidative damage in human erythrocytes exposed to the water-soluble free radical initiator 2.2’-azobis-2 amidinopropan dihydrochloride (AAPH). Materials and Methods: The reducing agent treatment efficacy was observed by evaluation of anion permeability for chloride, lipid peroxidation and hemolysis in red blood cells (RBCs). Anion permeability for chloride is an indicator of membrane protein damage and is evaluated in RBCs by the specific absorption of methemoglobin (CM) at 590 and 635 nm after treatment of heparinized blood with NaNO2. The measurement of the membrane lipid degradation is obtained by the determination of malondialdehyde. The lipid peroxidation susceptibility is observed after the oxidative stress induced by AAPH. The hemolysis assays are conducted on blood samples in phosphate buffer saline and the morphological changes of erythrocytes are observed by optical microscopy as membrane damage verification parameter. Results: Polyphenol treatment is associated with a significant increase in anion permeability for chloride compared with control and AAPH affected cells. Treatment with polyphenols was associated with a significant reduction in mean ± standard error of the mean membrane lipid peroxidation compared with control and AAPH treatment. Hemolysis data are also obtained in the previously described conditions. RBCs morphology data indeed confirm previous observations. Conclusion: In this study, it is evident that after in vitro oxidative damage of the membrane, red wine polyphenol extracts are as effective reducing agents also on CM indicator of membrane protein damages. Consequently, both red wine and polyphenol extracts both alone and mixed among them efficiently relieve the effects of oxidative stress.

Structure and insights into the function of a Ca(2+)-activated Cl(-) channel.

Bestrophin calcium-activated chloride channels (CaCCs) regulate the flow of chloride and other monovalent anions across cellular membranes in response to intracellular calcium (Ca(2+)) levels. Mutations in bestrophin 1 (BEST1) cause certain eye diseases. Here we present X-ray structures of chicken BEST1-Fab complexes, at 2.85 Å resolution, with permeant anions and Ca(2+). Representing, to our knowledge, the first structure of a CaCC, the eukaryotic BEST1 channel, which recapitulates CaCC function in liposomes, is formed from a pentameric assembly of subunits. Ca(2+) binds to the channel's large cytosolic region. A single ion pore, approximately 95 Å in length, is located along the central axis and contains at least 15 binding sites for anions. A hydrophobic neck within the pore probably forms the gate. Phenylalanine residues within it may coordinate permeating anions via anion-π interactions. Conformational changes observed near the 'Ca(2+) clasp' hint at the mechanism of Ca(2+)-dependent gating. Disease-causing mutations are prevalent within the gating apparatus.

EAAT2 (GLT-1; slc1a2) glutamate transporters reconstituted in liposomes argues against heteroexchange being substantially faster than net uptake.

The EAAT2 glutamate transporter, accounts for >90% of hippocampal glutamate uptake. Although EAAT2 is predominantly expressed in astrocytes, ∼10% of EAAT2 molecules are found in axon terminals. Despite the lower level of EAAT2 expression in glutamatergic terminals, when hippocampal slices are incubated with low concentration of d-aspartate (an EAAT2 substrate), axon terminals accumulate d-aspartate as quickly as astroglia. This implies an unexplained mismatch between the distribution of EAAT2 protein and of EAAT2-mediated transport activity. One hypothesis is that (1) heteroexchange of internal substrate with external substrate is considerably faster than net uptake and (2) terminals favor heteroexchange because of high levels of internal glutamate. However, it is currently unknown whether heteroexchange and uptake have similar or different rates. To address this issue, we used a reconstituted system to compare the relative rates of the two processes in rat and mice. Net uptake was sensitive to changes in the membrane potential and was stimulated by external permeable anions in agreement with the existence of an uncoupled anion conductance. By using the latter, we also demonstrate that the rate of heteroexchange also depends on the membrane potential. Additionally, our data further suggest the presence of a sodium leak in EAAT2. By incorporating the new findings in our previous model of glutamate uptake by EAAT2, we predict that the voltage sensitivity of exchange is caused by the voltage-dependent third Na(+) binding. Further, both our experiments and simulations suggest that the relative rates of net uptake and heteroexchange are comparable in EAAT2.

Behind the Scenes of CLC Gating: Deriving the Voltage Dependence of Membrane Proteins by Admittance Measurements

Behind the Scenes of CLC Gating: Deriving the Voltage Dependence of Membrane Proteins by Admittance Measurements