Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-05T05:09:54.224Z Has data issue: false hasContentIssue false
  • English
  • Français

Molecular biology and biophysical properties of ion channel gating pores

Published online by Cambridge University Press:  10 November 2014

Adrien Moreau ,
Pascal Gosselin-Badaroudine  and
Mohamed Chahine
Adrien Moreau
Affiliation:
Centre de recherche de l'institut universitaire en santé mentale de Québec, Quebec City, QC, CanadaG1J 2G3
Pascal Gosselin-Badaroudine
Affiliation:
Centre de recherche de l'institut universitaire en santé mentale de Québec, Quebec City, QC, CanadaG1J 2G3
Mohamed Chahine*
Affiliation:
Centre de recherche de l'institut universitaire en santé mentale de Québec, Quebec City, QC, CanadaG1J 2G3 Department of Medicine, Université Laval, Quebec City, QC, CanadaG1K 7P4
*
*Author for correspondence: Mohamed Chahine, Centre de recherche, Institut universitaire en santé mentale de Québec 2601 chemin de la Canardière, Quebec City, QC, CanadaG1J 2G3. Tel: 1-418-663-5747, ext. 4723; Fax: 1-418-663-8756; Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The voltage sensitive domain (VSD) is a pivotal structure of voltage-gated ion channels (VGICs) and plays an essential role in the generation of electrochemical signals by neurons, striated muscle cells, and endocrine cells. The VSD is not unique to VGICs. Recent studies have shown that a VSD regulates a phosphatase. Similarly, Hv1, a voltage-sensitive protein that lacks an apparent pore domain, is a self-contained voltage sensor that operates as an H+ channel.

VSDs are formed by four transmembrane helices (S1–S4). The S4 helix is positively charged due to the presence of arginine and lysine residues. It is surrounded by two water crevices that extend into the membrane from both the extracellular and intracellular milieus. A hydrophobic septum disrupts communication between these water crevices thus preventing the permeation of ions. The septum is maintained by interactions between the charged residues of the S4 segment and the gating charge transfer center. Mutating the charged residue of the S4 segment allows the water crevices to communicate and generate gating pore or omega pore. Gating pore currents have been reported to underlie several neuronal and striated muscle channelopathies. Depending on which charged residue on the S4 segment is mutated, gating pores are permeant either at depolarized or hyperpolarized voltages. Gating pores are cation selective and seem to converge toward Eisenmann's first or second selectivity sequences. Most gating pores are blocked by guanidine derivatives as well as trivalent and quadrivalent cations. Gating pores can be used to study the movement of the voltage sensor and could serve as targets for novel small therapeutic molecules.

Type
Review Article
Information
Quarterly Reviews of Biophysics , Volume 47 , Issue 4 , November 2014 , pp. 364 - 388
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

6. References

Aggarwal, S. K. & Mackinnon, R. (1996). Contribution of the S4 segment to gating charge in the Shaker K+ channel. Neuron 16, 1169–1177.Google Scholar
Ahern, C. A. & Horn, R. (2005). Focused electric field across the voltage sensor of potassium channels. Neuron 48, 25–29.Google Scholar
Amaral, C., Carnevale, V., Klein, M. L. & Treptow, W. (2012). Exploring conformational states of the bacterial voltage-gated sodium channel NavAb via molecular dynamics simulations. Proceedings of the National Academy of Sciences of the United States of America 109, 21336–21341.Google Scholar
Armstrong, C. M. & Bezanilla, F. (1973). Currents related to movement of the gating particles of the sodium channels. Nature 242, 459–461.Google Scholar
Armstrong, C. M. & Bezanilla, F. (1977). Inactivation of the sodium channel. II. Gating current experiments. The Journal of General Physiology 70, 567–590.Google Scholar
Banerjee, A. & Mackinnon, R. (2008). Inferred motions of the S3a helix during voltage-dependent K+ channel gating. Journal of Molecular Biology 381, 569–580.CrossRefGoogle ScholarPubMed
Batulan, Z., Haddad, G. A. & Blunck, R. (2010). An intersubunit interaction between S4–S5 linker and S6 is responsible for the slow off-gating component in Shaker K+ channels. The Journal of Biological Chemistry 285, 14005–14019.Google Scholar
Berger, T. K. & Isacoff, E. Y. (2011). The pore of the voltage-gated proton channel. Neuron 72, 991–1000.Google Scholar
Calcraft, P. J., Ruas, M., Pan, Z., Cheng, X., Arredouani, A., Hao, X., Tang, J., Rietdorf, K., Teboul, L., Chuang, K. T., Lin, P., Xiao, R., Wang, C., Zhu, Y., Lin, Y., Wyatt, C. N., Parrington, J., Ma, J., Evans, A. M., Galione, A. & Zhu, M. X. (2009). NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459, 596–600.Google Scholar
Campos, F. V., Chanda, B., Roux, B. & Bezanilla, F. (2007). Two atomic constraints unambiguously position the S4 segment relative to S1 and S2 segments in the closed state of Shaker K channel. Proceedings of the National Academy of Sciences of the United States of America 104, 7904–7909.Google Scholar
Capes, D. L., Arcisio-Miranda, M., Jarecki, B. W., French, R. J. & Chanda, B. (2012). Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor. Proceedings of the National Academy of Sciences of the United States of America 109, 2648–2653.CrossRefGoogle Scholar
Catterall, W. A. (1986). Molecular properties of voltage-sensitive sodium channels. Annual Review of Biochemistry 55, 953–985.Google Scholar
Catterall, W. A. (2011). Voltage-gated calcium channels. Cold Spring Harbor Perspectives in Biology 3, a003947.Google Scholar
Cestele, S. & Catterall, W. A. (2000). Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82, 883–892.Google Scholar
Cha, A., Ruben, P. C., George, A. L. Jr., Fujimoto, E. & Bezanilla, F. (1999). Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation. Neuron 22, 73–87.CrossRefGoogle Scholar
Chahine, M., Bennett, P. B., George, A. L. Jr. & Horn, R. (1994). Functional expression and properties of the human skeletal muscle sodium channel. Pflügers Archiv: European Journal of Physiology 427, 136–142.Google Scholar
Chanda, B. & Bezanilla, F. (2002). Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation. The Journal of General Physiology 120, 629–645.Google Scholar
Decoursey, T. E. (2013). Voltage-gated proton channels: molecular biology, physiology, and pathophysiology of the HV family. Physiological Reviews 93, 599–652.Google Scholar
Delemotte, L., Klein, M. L. & Tarek, M. (2012). Molecular dynamics simulations of voltage-gated cation channels: insights on voltage-sensor domain function and modulation. Frontiers in Pharmacology 3, 97.Google Scholar
Delemotte, L., Tarek, M., Klein, M. L., Amaral, C. & Treptow, W. (2011). Intermediate states of the Kv1.2 voltage sensor from atomistic molecular dynamics simulations. Proceedings of the National Academy of Sciences of the United States of America, 108, 6109–6114.Google Scholar
Delemotte, L., Treptow, W., Klein, M. L. & Tarek, M. (2010). Effect of sensor domain mutations on the properties of voltage-gated ion channels: molecular dynamics studies of the potassium channel Kv1.2. Biophysical Journal, 99, L72–74.Google Scholar
Eisenman, G. (1962). Cation selective glass electrodes and their mode of operation. Biophysical Journal 2(Pt 2), 259–323.Google Scholar
England, J. L. & Haran, G. (2011). Role of solvation effects in protein denaturation: from thermodynamics to single molecules and back. Annual Review of Physical Chemistry 62, 257–277.CrossRefGoogle ScholarPubMed
Fan, C., Lehmann-Horn, F., Weber, M. A., Bednarz, M., Groome, J. R., Jonsson, M. K. & Jurkat-Rott, K. (2013). Transient compartment-like syndrome and normokalaemic periodic paralysis due to a Ca(v)1.1 mutation. Brain 136(Pt 12), 3775–3786.Google Scholar
Francis, D. G., Rybalchenko, V., Struyk, A. & Cannon, S. C. (2011). Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia. Neurology 76, 1635–1641.CrossRefGoogle Scholar
Gamal El-Din, T. M., Heldstab, H., Lehmann, C. & Greeff, N. G. (2010). Double gaps along Shaker S4 demonstrate omega currents at three different closed states. Channels (Austin) 4, 93–100.Google Scholar
Gao, Z., Zhang, T., Wu, M., Xiong, Q., Sun, H., Zhang, Y., Zu, L., Wang, W. & Li, M. (2010). Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug–channel interactions. Journal of Biological Chemistry 285, 28322–28332.Google Scholar
Gonzalez, C., Baez-Nieto, D., Valencia, I., Oyarzun, I., Rojas, P., Naranjo, D. & Latorre, R. (2012). K(+) channels: function–structural overview. Comprehensive Physiology 2, 2087–2149.Google Scholar
Goodchild, S. J. & Fedida, D. (2012). Contributions of intracellular ions to kv channel voltage sensor dynamics. Frontiers in Pharmacology 3, 114.Google Scholar
Gosselin-Badaroudine, P., Delemotte, L., Moreau, A., Klein, M. L. & Chahine, M. (2012a). Gating pore currents and the resting state of Nav1.4 voltage sensor domains. Proceedings of the National Academy of Sciences of the United States of America 109, 19250–19255.Google Scholar
Gosselin-Badaroudine, P., Keller, D. I., Huang, H., Pouliot, V., Chatelier, A., Osswald, S., Brink, M. & Chahine, M. (2012b). A proton leak current through the cardiac sodium channel is linked to mixed arrhythmia and the dilated cardiomyopathy phenotype. PLoS ONE 7, e38331.Google Scholar
Gosselin-Badaroudine, P., Moreau, A. & Chahine, M. (2013). Na 1.5 mutations linked to dilated cardiomyopathy phenotypes: Is the gating pore current the missing link? Channels (Austin) 8, 1–5.Google Scholar
Groome, J. R., Lehmann-Horn, F., Fan, C., Wolf, M., Winston, V., Merlini, L. & Jurkat-Rott, K. (2014). Nav1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4 movement during recovery. Brain 137, 998–1008.Google Scholar
Guy, H. R. & Seetharamulu, P. (1986). Molecular model of the action potential sodium channel. Proceedings of the National Academy of Sciences of the United States of America 83, 508–512.Google Scholar
Henrion, U., Renhorn, J., Borjesson, S. I., Nelson, E. M., Schwaiger, C. S., Bjelkmar, P., Wallner, B., Lindahl, E. & Elinder, F. (2012). Tracking a complete voltage-sensor cycle with metal–ion bridges. Proceedings of the National Academy of Sciences of the United States of America 109, 8552–8557.Google Scholar
Hodgkin, A. L. & Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. Journal of Physiology 117, 500–544.Google Scholar
Hong, L., Kim, I. H. & Tombola, F. (2014). Molecular determinants of Hv1 proton channel inhibition by guanidine derivatives. Proceedings of the National Academy of Sciences of the United States of America 111, 9971–9976.Google Scholar
Hong, L., Pathak, M. M., Kim, I. H., Ta, D. & Tombola, F. (2013). Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains. Neuron 77, 274–287.Google Scholar
Ishibashi, K., Suzuki, M. & Imai, M. (2000). Molecular cloning of a novel form (two-repeat) protein related to voltage-gated sodium and calcium channels. Biochemical and Biophysical Research Communications 270, 370–376.Google Scholar
Jensen, M. O., Jogini, V., Borhani, D. W., Leffler, A. E., Dror, R. O. & Shaw, D. E. (2012). Mechanism of voltage gating in potassium channels. Science 336, 229–233.Google Scholar
Jiang, Y., Lee, A., Chen, J., Ruta, V., Cadene, M., Chait, B. T. & Mackinnon, R. (2003). X-ray structure of a voltage-dependent K+ channel. Nature 423, 33–41.Google Scholar
Khalili-Araghi, F., Tajkhorshid, E., Roux, B. & Schulten, K. (2012). Molecular dynamics investigation of the omega-current in the Kv1.2 voltage sensor domains. Biophysical Journal 102, 258–267.Google Scholar
Klassen, T. L., Spencer, A. N. & Gallin, W. J. (2008). A naturally occurring omega current in a Kv3 family potassium channel from a platyhelminth. BMC Neuroscience 9, 52.Google Scholar
Koopmann, T. T., Bezzina, C. R. & Wilde, A. A. (2006). Voltage-gated sodium channels: action players with many faces. Annals of Medicine 38, 472–482.Google Scholar
Kuzmenkin, A., Bezanilla, F. & Correa, A. M. (2004). Gating of the bacterial sodium channel, NaChBac: voltage-dependent charge movement and gating currents. The Journal of General Physiology 124, 349–356.Google Scholar
Lacroix, J. J., Campos, F. V., Frezza, L. & Bezanilla, F. (2013). Molecular bases for the asynchronous activation of sodium and potassium channels required for nerve impulse generation. Neuron 79, 651–657.Google Scholar
Leipold, E., Debie, H., Zorn, S., Borges, A., Olivera, B. M., Terlau, H. & Heinemann, S. H. (2007). muO conotoxins inhibit NaV channels by interfering with their voltage sensors in domain-2. Channels (Austin), 1, 253–262.Google Scholar
Li, P., Chen, Z., Xu, H., Sun, H., Li, H., Liu, H., Yang, H., Gao, Z., Jiang, H. & Li, M. (2013). The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands. Cell Research 23, 1106–1118.Google Scholar
Li, Q., Wanderling, S., Paduch, M., Medovoy, D., Singharoy, A., Mcgreevy, R., Villalba-Galea, C. A., Hulse, R. E., Roux, B., Schulten, K., Kossiakoff, A. & Perozo, E. (2014). Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. Nature Structural and Molecular Biology 21, 244–252.CrossRefGoogle Scholar
Lin, M. C., Hsieh, J. Y., Mock, A. F. & Papazian, D. M. (2011). R1 in the Shaker S4 occupies the gating charge transfer center in the resting state. The Journal of General Physiology 138, 155–163.Google Scholar
Long, S. B., Campbell, E. B. & Mackinnon, R. (2005). Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309, 903–908.CrossRefGoogle ScholarPubMed
Long, S. B., Tao, X., Campbell, E. B. & Mackinnon, R. (2007). Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. Nature 450, 376–382.Google Scholar
Mannikko, R., Elinder, F. & Larsson, H. P. (2002). Voltage-sensing mechanism is conserved among ion channels gated by opposite voltages. Nature 419, 837–841.Google Scholar
Mannikko, R., Pandey, S., Larsson, H. P. & Elinder, F. (2005). Hysteresis in the voltage dependence of HCN channels: conversion between two modes affects pacemaker properties. The Journal of General Physiology 125, 305–326.Google Scholar
Marcus, Y. (2012). The guanidinium ion. The Journal of Chemical Thermodynamics 48, 70–74.Google Scholar
Matthews, E., Labrum, R., Sweeney, M. G., Sud, R., Haworth, A., Chinnery, P. F., Meola, G., Schorge, S., Kullmann, D. M., Davis, M. B. & Hanna, M. G. (2009). Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. Neurology 72, 1544–1547.Google Scholar
Mccusker, E. C., Bagneris, C., Naylor, C. E., Cole, A. R., D'Avanzo, N., Nichols, C. G. & Wallace, B. A. (2012). Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing. Nature Communications 3, 1102.CrossRefGoogle ScholarPubMed
Misra, S. N., Kahlig, K. M. & George, A. L. Jr. (2008). Impaired Nav1.2 function and reduced cell surface expression in benign familial neonatal-infantile seizures. Epilepsia 49, 1535–1545.Google Scholar
Moreau, A., Gosselin-Badaroudine, P. & Chahine, M. (2014). Biophysics, pathophysiology, and pharmacology of ion channel gating pores. Frontiers in Pharmacology 5, 53.CrossRefGoogle ScholarPubMed
Murata, Y., Iwasaki, H., Sasaki, M., Inaba, K. & Okamura, Y. (2005). Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor. Nature 435, 1239–1243.Google Scholar
Musset, B., Smith, S. M., Rajan, S., Morgan, D., Cherny, V. V. & Decoursey, T. E. (2011). Aspartate 112 is the selectivity filter of the human voltage-gated proton channel. Nature 480, 273–277.Google Scholar
Nilius, B. & Owsianik, G. (2011). The transient receptor potential family of ion channels. Genome Biology 12, 218.Google Scholar
Noda, M., Shimizu, S., Tanabe, T., Takai, T., Kayano, T., Ikeda, T., Takahashi, H., Nakayama, H., Kanaoka, Y., Minamino, N., Kangawa, K., Matsuo, H., Raftery, M. A., Hirose, T., Inayama, S., Hayashida, H., Miyat, T. & Numa, S. (1984). Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312, 121–127.Google Scholar
Olcese, R., Latorre, R., Toro, L., Bezanilla, F. & Stefani, E. (1997). Correlation between charge movement and ionic current during slow inactivation in Shaker K+ channels. The Journal of General Physiology 110, 579–589.Google Scholar
Payandeh, J., Gamal El-Din, T. M., Scheuer, T., Zheng, N. & Catterall, W. A. (2012). Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. Nature 486, 135–139.Google Scholar
Payandeh, J., Scheuer, T., Zheng, N. & Catterall, W. A. (2011). The crystal structure of a voltage-gated sodium channel. Nature 475, 353–358.Google Scholar
Peretz, A., Pell, L., Gofman, Y., Haitin, Y., Shamgar, L., Patrich, E., Kornilov, P., Gourgy-Hacohen, O., Ben-Tal, N. & Attali, B. (2010). Targeting the voltage sensor of Kv7.2 voltage-gated K+ channels with a new gating-modifier. Proceedings of the National Academy of Sciences of the United States of America 107, 15637–15642.CrossRefGoogle ScholarPubMed
Piper, D. R., Varghese, A., Sanguinetti, M. C. & Tristani-Firouzi, M. (2003). Gating currents associated with intramembrane charge displacement in HERG potassium channels. Proceedings of the National Academy of Sciences of the United States of America 100, 10534–10539.Google Scholar
Pless, S. A., Galpin, J. D., Niciforovic, A. P. & Ahern, C. A. (2011). Contributions of counter-charge in a potassium channel voltage-sensor domain. Nature Chemical Biology 7, 617–623.CrossRefGoogle Scholar
Pomes, R. & Roux, B. (2002). Molecular mechanism of H+ conduction in the single-file water chain of the gramicidin channel. Biophysical Journal 82, 2304–2316.Google Scholar
Posson, D. J., Ge, P., Miller, C., Bezanilla, F. & Selvin, P. R. (2005). Small vertical movement of a K+ channel voltage sensor measured with luminescence energy transfer. Nature 436, 848–851.Google Scholar
Quill, T. A., Sugden, S. A., Rossi, K. L., Doolittle, L. K., Hammer, R. E. & Garbers, D. L. (2003). Hyperactivated sperm motility driven by CatSper2 is required for fertilization. Proceedings of the National Academy of Sciences of the United States of America 100, 14869–14874.CrossRefGoogle ScholarPubMed
Ramsey, I. S., Mokrab, Y., Carvacho, I., Sands, Z. A., Sansom, M. S. & Clapham, D. E. (2010). An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1. Nature Structural and Molecular Biology 17, 869–875.Google Scholar
Ren, D., Navarro, B., Perez, G., Jackson, A. C., Hsu, S., Shi, Q., Tilly, J. L. & Clapham, D. E. (2001). A sperm ion channel required for sperm motility and male fertility. Nature 413, 603–609.Google Scholar
Sasaki, M., Takagi, M. & Okamura, Y. (2006). A voltage sensor-domain protein is a voltage-gated proton channel. Science 312, 589–592.Google Scholar
Seoh, S. A., Sigg, D., Papazian, D. M. & Bezanilla, F. (1996). Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel. Neuron 16, 1159–1167.Google Scholar
Shirokov, R., Levis, R., Shirokova, N. & Rios, E. (1992). Two classes of gating current from L-type Ca channels in guinea pig ventricular myocytes. The Journal of General Physiology 99, 863–895.Google Scholar
Sigworth, F. J. (1994). Voltage gating of ion channels. Quarterly Reviews of Biophysics 27, 1–40.Google Scholar
Sokolov, S., Scheuer, T. & Catterall, W. A. (2005). Ion permeation through a voltage-sensitive gating pore in brain sodium channels having voltage sensor mutations. Neuron 47, 183–189.CrossRefGoogle ScholarPubMed
Sokolov, S., Scheuer, T. & Catterall, W. A. (2007). Gating pore current in an inherited ion channelopathy. Nature 446, 76–78.Google Scholar
Sokolov, S., Scheuer, T. & Catterall, W. A. (2008). Depolarization-activated gating pore current conducted by mutant sodium channels in potassium-sensitive normokalemic periodic paralysis. Proceedings of the National Academy of Sciences of the United States of America 105, 19980–19985.Google Scholar
Sokolov, S., Scheuer, T. & Catterall, W. A. (2010). Ion permeation and block of the gating pore in the voltage sensor of NaV1.4 channels with hypokalemic periodic paralysis mutations. The Journal of General Physiology 136, 225–236.Google Scholar
Starace, D. M. & Bezanilla, F. (2004). A proton pore in a potassium channel voltage sensor reveals a focused electric field. Nature 427, 548–553.Google Scholar
Starace, D. M., Stefani, E. & Bezanilla, F. (1997). Voltage-dependent proton transport by the voltage sensor of the Shaker K+ channel. Neuron 19, 1319–1327.Google Scholar
Stevens, M., Peigneur, S. & Tytgat, J. (2011). Neurotoxins and their binding areas on voltage-gated sodium channels. Frontiers in Pharmacology 2, 71.Google Scholar
Struyk, A. F. & Cannon, S. C. (2007). A Na+ channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore. The Journal of General Physiology 130, 11–20.Google Scholar
Struyk, A. F., Markin, V. S., Francis, D. & Cannon, S. C. (2008). Gating pore currents in DIIS4 mutations of NaV1.4 associated with periodic paralysis: saturation of ion flux and implications for disease pathogenesis. The Journal of General Physiology 132, 447–464.Google Scholar
Stuhmer, W., Conti, F., Suzuki, H., Wang, X. D., Noda, M., Yahagi, N., Kubo, H. & Numa, S. (1989). Structural parts involved in activation and inactivation of the sodium channel. Nature 339, 597–603.CrossRefGoogle ScholarPubMed
Takeshita, K., Sakata, S., Yamashita, E., Fujiwara, Y., Kawanabe, A., Kurokawa, T., Okochi, Y., Matsuda, M., Narita, H., Okamura, Y. & Nakagawa, A. (2014). X-ray crystal structure of voltage-gated proton channel. Nature Structural and Molecular Biology 21, 352–357.Google Scholar
Tao, X., Lee, A., Limapichat, W., Dougherty, D. A. & Mackinnon, R. (2010). A gating charge transfer center in voltage sensors. Science 328, 67–73.Google Scholar
Tombola, F., Pathak, M. M., Gorostiza, P. & Isacoff, E. Y. (2007). The twisted ion-permeation pathway of a resting voltage-sensing domain. Nature 445, 546–549.Google Scholar
Tombola, F., Pathak, M. M. & Isacoff, E. Y. (2005). Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores. Neuron 45, 379–388.Google Scholar
Vargas, E., Yarov-Yarovoy, V., Khalili-Araghi, F., Catterall, W. A., Klein, M. L., Tarek, M., Lindahl, E., Schulten, K., Perozo, E., Bezanilla, F. & Roux, B. (2012). An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations. The Journal of General Physiology 140, 587–594.CrossRefGoogle ScholarPubMed
Villalba-Galea, C. A., Sandtner, W., Starace, D. M. & Bezanilla, F. (2008). S4-based voltage sensors have three major conformations. Proceedings of the National Academy of Sciences of the United States of America 105, 17600–17607.Google Scholar
Volkers, L., Kahlig, K. M., Verbeek, N. E., Das, J. H., Van Kempen, M. J., Stroink, H., Augustijn, P., Van Nieuwenhuizen, O., Lindhout, D., George, A. L. Jr., Koeleman, B. P. & Rook, M. B. (2011). Nav 1.1 dysfunction in genetic epilepsy with febrile seizures-plus or Dravet syndrome. European Journal of Neuroscience 34, 1268–1275.Google Scholar
Wang, X., Zhang, X., Dong, X. P., Samie, M., Li, X., Cheng, X., Goschka, A., Shen, D., Zhou, Y., Harlow, J., Zhu, M. X., Clapham, D. E., Ren, D. & Xu, H. (2012). TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes. Cell 151, 372–383.Google Scholar
Wuttke, T. V., Jurkat-Rott, K., Paulus, W., Garncarek, M., Lehmann-Horn, F. & Lerche, H. (2007). Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations. Neurology 69, 2045–2053.Google Scholar
Xiao, Y., Blumenthal, K. M. & Cummins, T. R. (2014). Gating pore currents demonstrate selective and specific modulation of individual sodium channel voltage sensors by biological toxins. Molecular Pharmacology 86, 159–167.Google Scholar
Yang, N., George, A. L. Jr. & Horn, R. (1996). Molecular basis of charge movement in voltage-gated sodium channels. Neuron 16, 113–122.Google Scholar
Yang, N. & Horn, R. (1995). Evidence for voltage-dependent S4 movement in sodium channels. Neuron 15, 213–218.Google Scholar
Yu, F. H. & Catterall, W. A. (2004). The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Science's STKE: Signal Transduction Knowledge Environment 2004, re15.Google Scholar
Yu, F. H., Yarov-Yarovoy, V., Gutman, G. A. & Catterall, W. A. (2005). Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacological Reviews 57, 387–395.Google Scholar
Yuan, A., Santi, C. M., Wei, A., Wang, Z. W., Pollak, K., Nonet, M., Kaczmarek, L., Crowder, C. M. & Salkoff, L. (2003). The sodium-activated potassium channel is encoded by a member of the Slo gene family. Neuron 37, 765–773.CrossRefGoogle ScholarPubMed
Zhang, X., Ren, W., Decaen, P., Yan, C., Tao, X., Tang, L., Wang, J., Hasegawa, K., Kumasaka, T., He, J., Wang, J., Clapham, D. E. & Yan, N. (2012). Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature 486, 130–134.Google Scholar