1932

Abstract

Carefully orchestrated opening and closing of ion channels control the diffusion of ions across cell membranes, generating the electrical signals required for fast transmission of information throughout the nervous system. Inactivation is a parsimonious means for channels to restrict ion conduction without the need to remove the activating stimulus. Voltage-gated channel inactivation plays crucial physiological roles, such as controlling action potential duration and firing frequency in neurons. The ball-and-chain moniker applies to a type of inactivation proposed first for sodium channels and later shown to be a universal mechanism. Still, structural evidence for this mechanism remained elusive until recently. We review the ball-and-chain inactivation research starting from its introduction as a crucial component of sodium conductance during electrical signaling in the classical Hodgkin and Huxley studies, through the discovery of its simple intuitive mechanism in potassium channels during the molecular cloning era, to the eventual elucidation of a potassium channel structure in a ball-and-chain inactivated state.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-100322-072921
2023-05-09
2024-10-14
Loading full text...

Full text loading...

/deliver/fulltext/biophys/52/1/annurev-biophys-100322-072921.html?itemId=/content/journals/10.1146/annurev-biophys-100322-072921&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Ahern CA. 2013. What activates inactivation?. J. Gen. Physiol. 142:97–100
    [Google Scholar]
  2. 2.
    Aldrich RW. 2001. Fifty years of inactivation. Nature 411:643–44
    [Google Scholar]
  3. 3.
    Aldrich RW, Corey DP, Stevens CF. 1983. A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature 306:436–41
    [Google Scholar]
  4. 4.
    Aldrich RW, Hoshi T, Zagotta WN. 1990. Differences in gating among amino-terminal variants of Shaker potassium channels. Cold Spring Harb. Symp. Quant. Biol. 55:19–27
    [Google Scholar]
  5. 5.
    Antz C, Bauer T, Kalbacher H, Frank R, Covarrubias M et al. 1999. Control of K+ channel gating by protein phosphorylation: structural switches of the inactivation gate. Nat. Struct. Biol. 6:146–50
    [Google Scholar]
  6. 6.
    Antz C, Fakler B. 1998. Fast inactivation of voltage-gated K+ channels: from cartoon to structure. News Physiol. Sci. 13:177–82
    [Google Scholar]
  7. 7.
    Antz C, Geyer M, Fakler B, Schott MK, Guy HR et al. 1997. NMR structure of inactivation gates from mammalian voltage-dependent potassium channels. Nature 385:272–75
    [Google Scholar]
  8. 8.
    Armstrong CM. 1966. Time course of TEA+-induced anomalous rectification in squid giant axons. J. Gen. Physiol. 50:491–503
    [Google Scholar]
  9. 9.
    Armstrong CM. 1968. Induced inactivation of the potassium permeability of squid axon membranes. Nature 219:1262–63
    [Google Scholar]
  10. 10.
    Armstrong CM. 1969. Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons. J. Gen. Physiol. 54:553–75
    [Google Scholar]
  11. 11.
    Armstrong CM. 1981. Sodium channels and gating currents. Physiol. Rev. 61:644–83
    [Google Scholar]
  12. 12.
    Armstrong CM, Bezanilla F. 1977. Inactivation of the sodium channel. II. Gating current experiments. J. Gen. Physiol. 70:567–90
    [Google Scholar]
  13. 13.
    Armstrong CM, Bezanilla F, Rojas E. 1973. Destruction of sodium conductance inactivation in squid axons perfused with pronase. J. Gen. Physiol. 62:375–91
    [Google Scholar]
  14. 14.
    Bahring R, Vardanyan V, Pongs O. 2004. Differential modulation of Kv1 channel-mediated currents by co-expression of Kvβ3 subunit in a mammalian cell-line. Mol. Membr. Biol. 21:19–25
    [Google Scholar]
  15. 15.
    Baker K, Salkoff L 1990. The Drosophila Shaker gene codes for a distinctive K+ current in a subset of neurons. Neuron 4:129–40
    [Google Scholar]
  16. 16.
    Baukrowitz T, Yellen G. 1995. Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms. Neuron 15:951–60
    [Google Scholar]
  17. 17.
    Baukrowitz T, Yellen G. 1996. Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel. Science 271:653–56
    [Google Scholar]
  18. 18.
    Benarroch EE. 2015. Ion channels in nociceptors: recent developments. Neurology 84:1153–64
    [Google Scholar]
  19. 19.
    Bentrop D, Beyermann M, Wissmann R, Fakler B. 2001. NMR structure of the “ball-and-chain” domain of KCNMB2, the β 2-subunit of large conductance Ca2+- and voltage-activated potassium channels. J. Biol. Chem. 276:42116–21
    [Google Scholar]
  20. 20.
    Bett GC, Dinga-Madou I, Zhou Q, Bondarenko VE, Rasmusson RL. 2011. A model of the interaction between N-type and C-type inactivation in Kv1.4 channels. Biophys. J. 100:11–21
    [Google Scholar]
  21. 21.
    Boiteux C, Posson DJ, TW Allen, Nimigean CM. 2020. Selectivity filter ion binding affinity determines inactivation in a potassium channel. PNAS 117:29968–78
    [Google Scholar]
  22. 22.
    Catterall WA. 2000. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26:13–25
    [Google Scholar]
  23. 23.
    Catterall WA, Goldin AL, Waxman SG. 2005. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol. Rev. 57:397–409
    [Google Scholar]
  24. 24.
    Chen J, Winston JH, Sarna SK. 2013. Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats. Neuroscience 248:469–78
    [Google Scholar]
  25. 25.
    Chen R, Li YJ, Li JQ, Lv XX, Chen SZ et al. 2011. Electrical injury alters ion channel expression levels and electrophysiological properties in rabbit dorsal root ganglia neurons. Burns 37:304–11
    [Google Scholar]
  26. 26.
    Chien LY, Cheng JK, Chu D, Cheng CF, Tsaur ML. 2007. Reduced expression of A-type potassium channels in primary sensory neurons induces mechanical hypersensitivity. J. Neurosci. 27:9855–65
    [Google Scholar]
  27. 27.
    Choi KL, Aldrich RW, Yellen G. 1991. Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels. PNAS 88:5092–95
    [Google Scholar]
  28. 28.
    Coburger I, Yang K, Bernert A, Wiesel E, Sahoo N et al. 2020. Impact of intracellular hemin on N-type inactivation of voltage-gated K+ channels. Pflugers Arch. 472:551–60
    [Google Scholar]
  29. 29.
    Colwell CS. 2006. BK channels and circadian output. Nat. Neurosci. 9:985–86
    [Google Scholar]
  30. 30.
    Connor JA, Stevens CF. 1971. Voltage clamp studies of a transient outward membrane current in gastropod neural somata. J. Physiol. 213:21–30
    [Google Scholar]
  31. 31.
    Cordero-Morales JF, Cuello LG, Perozo E. 2006. Voltage-dependent gating at the KcsA selectivity filter. Nat. Struct. Mol. Biol. 13:319–22
    [Google Scholar]
  32. 32.
    Cordero-Morales JF, Jogini V, Lewis A, Vasquez V, Cortes DM et al. 2007. Molecular driving forces determining potassium channel slow inactivation. Nat. Struct. Mol. Biol. 14:1062–69
    [Google Scholar]
  33. 33.
    Cuello LG, Jogini V, Cortes DM, Perozo E. 2010. Structural mechanism of C-type inactivation in K+ channels. Nature 466:203–8
    [Google Scholar]
  34. 34.
    Dart C. 2010. Lipid microdomains and the regulation of ion channel function. J. Physiol. 588:3169–78
    [Google Scholar]
  35. 35.
    Demo SD, Yellen G. 1991. The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker. Neuron 7:743–53
    [Google Scholar]
  36. 36.
    Dong J, Shi N, Berke I, Chen L, Jiang Y 2005. Structures of the MthK RCK domain and the effect of Ca2+ on gating ring stability. J. Biol. Chem. 280:41716–24
    [Google Scholar]
  37. 37.
    Duan KZ, Xu Q, Zhang XM, Zhao ZQ, Mei YA, Zhang YQ. 2012. Targeting A-type K+ channels in primary sensory neurons for bone cancer pain in a rat model. Pain 153:562–74
    [Google Scholar]
  38. 38.
    Fan C, Sukomon N, Flood E, Rheinberger J, Allen TW, Nimigean CM. 2020. Ball-and-chain inactivation in a calcium-gated potassium channel. Nature 580:288–93
    [Google Scholar]
  39. 39.
    Foster CD, Chung S, Zagotta WN, Aldrich RW, Levitan IB. 1992. A peptide derived from the shaker B K+ channel produces short and long blocks of reconstituted Ca2+-dependent K+ channels. Neuron 9:229–36
    [Google Scholar]
  40. 40.
    Geiger JR, Jonas P 2000. Dynamic control of presynaptic Ca2+ inflow by fast-inactivating K+ channels in hippocampal mossy fiber boutons. Neuron 28:927–39
    [Google Scholar]
  41. 41.
    Gillette MU, Tischkau SA. 1999. Suprachiasmatic nucleus: the brain's circadian clock. Recent Prog. Horm. Res. 54: 33–58:; discussion 58–59
    [Google Scholar]
  42. 42.
    Goldin AL. 2003. Mechanisms of sodium channel inactivation. Curr. Opin. Neurobiol. 13:284–90
    [Google Scholar]
  43. 43.
    Gonzalez-Perez V, Lingle CJ. 2019. Regulation of BK channels by β and γ subunits. Annu. Rev. Physiol. 81:113–37
    [Google Scholar]
  44. 44.
    Gonzalez-Perez V, Zeng XH, Henzler-Wildman K, Lingle CJ. 2012. Stereospecific binding of a disordered peptide segment mediates BK channel inactivation. Nature 485:133–36
    [Google Scholar]
  45. 45.
    Gulbis JM, Zhou M, Mann S, MacKinnon R. 2000. Structure of the cytoplasmic β subunit-T1 assembly of voltage-dependent K+ channels. Science 289:123–27
    [Google Scholar]
  46. 46.
    Haberberger RV, Barry C, Dominguez N, Matusica D. 2019. Human dorsal root ganglia. Front Cell Neurosci 13:271
    [Google Scholar]
  47. 47.
    Heginbotham L, Abramson T, MacKinnon R. 1992. A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels. Science 258:1152–55
    [Google Scholar]
  48. 48.
    Heginbotham L, Lu Z, Abramson T, MacKinnon R. 1994. Mutations in the K+ channel signature sequence. Biophys. J. 66:1061–67
    [Google Scholar]
  49. 49.
    Heinemann SH, Hoshi T. 2006. Multifunctional potassium channels: electrical switches and redox enzymes, all in one. Sci. STKE 2006.pe33
    [Google Scholar]
  50. 50.
    Heinemann SH, Rettig J, Wunder F, Pongs O. 1995. Molecular and functional characterization of a rat brain Kvβ3 potassium channel subunit. FEBS Lett. 377:383–89
    [Google Scholar]
  51. 51.
    Helliwell KE, Chrachri A, Koester JA, Wharam S, Taylor AR et al. 2020. A novel single-domain Na+-selective voltage-gated channel in photosynthetic eukaryotes. Plant Physiol. 184:1674–83
    [Google Scholar]
  52. 52.
    Helliwell KE, Chrachri A, Koester JA, Wharam S, Verret F et al. 2019. Alternative mechanisms for fast Na+/Ca2+ signaling in eukaryotes via a novel class of single-domain voltage-gated channels. Curr. Biol. 29:1503–11.e6
    [Google Scholar]
  53. 53.
    Hille B. 1978. Ionic channels in excitable membranes. Current problems and biophysical approaches. Biophys. J. 22:283–94
    [Google Scholar]
  54. 54.
    Hille B. 2001. Ion Channels of Excitable Membranes Sunderland, MA: Sinauer Assoc.
    [Google Scholar]
  55. 55.
    Hodgkin AL, Huxley AF. 1952. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117:500–44
    [Google Scholar]
  56. 56.
    Hoshi T, Zagotta WN, Aldrich RW. 1990. Biophysical and molecular mechanisms of Shaker potassium channel inactivation. Science 250:533–38
    [Google Scholar]
  57. 57.
    Hoshi T, Zagotta WN, Aldrich RW. 1991. Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region. Neuron 7:547–56
    [Google Scholar]
  58. 58.
    Huang CY, Lien CC, Cheng CF, Yen TY, Chen CJ, Tsaur ML. 2017. K+ channel Kv3.4 is essential for axon growth by limiting the influx of Ca2+ into growth cones. J. Neurosci. 37:4433–49
    [Google Scholar]
  59. 59.
    Hyndman D, Bauman DR, Heredia VV, Penning TM. 2003. The aldo-keto reductase superfamily homepage. Chem. Biol. Interact. 143–44:621–31
    [Google Scholar]
  60. 60.
    Isacoff EY, Jan YN, Jan LY 1991. Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel. Nature 353:86–90
    [Google Scholar]
  61. 61.
    Jan LY, Jan YN. 1992. Structural elements involved in specific K+ channel functions. Annu. Rev. Physiol. 54:537–55
    [Google Scholar]
  62. 62.
    Jiang D, Shi H, Tonggu L, Gamal El-Din TM, Lenaeus MJ et al. 2020. Structure of the cardiac sodium channel. Cell 180:122–34.e10
    [Google Scholar]
  63. 63.
    Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R. 2002. Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417:515–22
    [Google Scholar]
  64. 64.
    Kim DS, Choi JO, Rim HD, Cho HJ. 2002. Downregulation of voltage-gated potassium channel α gene expression in dorsal root ganglia following chronic constriction injury of the rat sciatic nerve. Brain Res. Mol. Brain Res. 105:146–52
    [Google Scholar]
  65. 65.
    Koishi R, Xu H, Ren D, Navarro B, Spiller BW et al. 2004. A superfamily of voltage-gated sodium channels in bacteria. J. Biol. Chem. 279:9532–38
    [Google Scholar]
  66. 66.
    Kramer RH, Goulding E, Siegelbaum SA. 1994. Potassium channel inactivation peptide blocks cyclic nucleotide-gated channels by binding to the conserved pore domain. Neuron 12:655–62
    [Google Scholar]
  67. 67.
    Kreusch A, Pfaffinger PJ, Stevens CF, Choe S. 1998. Crystal structure of the tetramerization domain of the Shaker potassium channel. Nature 392:945–48
    [Google Scholar]
  68. 68.
    Kuo MM, Maslennikov I, Molden B, Choe S. 2008. The desensitization gating of the MthK K+ channel is governed by its cytoplasmic amino terminus. PLOS Biol. 6:e223
    [Google Scholar]
  69. 69.
    Kurata HT, Fedida D. 2006. A structural interpretation of voltage-gated potassium channel inactivation. Prog. Biophys. Mol. Biol. 92:185–208
    [Google Scholar]
  70. 70.
    Li Q, Yan J 2016. Modulation of BK channel function by auxiliary β and γ subunits. Int. Rev. Neurobiol. 128:51–90
    [Google Scholar]
  71. 71.
    Li Y, Berke I, Chen L, Jiang Y 2007. Gating and inward rectifying properties of the MthK K+ channel with and without the gating ring. J. Gen. Physiol. 129:109–20
    [Google Scholar]
  72. 72.
    Lingle CJ, Zeng XH, Ding JP, Xia XM. 2001. Inactivation of BK channels mediated by the NH2 terminus of the β3b auxiliary subunit involves a two-step mechanism: possible separation of binding and blockade. J. Gen. Physiol. 117:583–605
    [Google Scholar]
  73. 73.
    Lo MV, Shrager P. 1981. Block and inactivation of sodium channels in nerve by amino acid derivatives. II. Dependence on temperature and drug concentration. Biophys. J. 35:45–57
    [Google Scholar]
  74. 74.
    Long SB, Campbell EB, MacKinnon R. 2005. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309:897–903
    [Google Scholar]
  75. 75.
    Lopez-Barneo J, Hoshi T, Heinemann SH, Aldrich RW. 1993. Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels. Recept. Channels 1:161–71
    [Google Scholar]
  76. 76.
    MacKinnon R, Aldrich RW, Lee AW. 1993. Functional stoichiometry of Shaker potassium channel inactivation. Science 262:757–59
    [Google Scholar]
  77. 77.
    Matulef K, Annen AW, Nix JC, Valiyaveetil FI. 2016. Individual ion binding sites in the K+ channel play distinct roles in C-type inactivation and in recovery from inactivation. Structure 24:750–61
    [Google Scholar]
  78. 78.
    McCormack T, McCormack K. 1994. Shaker K+ channel β subunits belong to an NAD(P)H-dependent oxidoreductase superfamily. Cell 79:1133–35
    [Google Scholar]
  79. 79.
    Meredith AL, Wiler SW, Miller BH, Takahashi JS, Fodor AA et al. 2006. BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output. Nat. Neurosci. 9:1041–49
    [Google Scholar]
  80. 80.
    Molina ML, Barrera FN, Encinar JA, Renart ML, Fernandez AM et al. 2008. N-type inactivation of the potassium channel KcsA by the Shaker B “ball” peptide: mapping the inactivating peptide-binding epitope. J. Biol. Chem. 283:18076–85
    [Google Scholar]
  81. 81.
    Montgomery JR, Meredith AL. 2012. Genetic activation of BK currents in vivo generates bidirectional effects on neuronal excitability. PNAS 109:18997–9002
    [Google Scholar]
  82. 82.
    Montgomery JR, Whitt JP, Wright BN, Lai MH, Meredith AL. 2013. Mis-expression of the BK K+ channel disrupts suprachiasmatic nucleus circuit rhythmicity and alters clock-controlled behavior. Am. J. Physiol. Cell Physiol. 304:C299–311
    [Google Scholar]
  83. 83.
    Muqeem T, Ghosh B, Pinto V, Lepore AC, Covarrubias M. 2018. Regulation of nociceptive glutamatergic signaling by presynaptic Kv3.4 channels in the rat spinal dorsal horn. J. Neurosci. 38:3729–40
    [Google Scholar]
  84. 84.
    Murrell-Lagnado RD, Aldrich RW 1993. Interactions of amino terminal domains of Shaker K channels with a pore blocking site studied with synthetic peptides. J. Gen. Physiol. 102:949–75
    [Google Scholar]
  85. 85.
    Nakajima S. 1966. Analysis of K inactivation and TEA action in the supramedullary cells of puffer. J. Gen. Physiol. 49:629–40
    [Google Scholar]
  86. 86.
    Nascimento AI, Mar FM, Sousa MM. 2018. The intriguing nature of dorsal root ganglion neurons: linking structure with polarity and function. Prog. Neurobiol. 168:86–103
    [Google Scholar]
  87. 87.
    Nonner W. 1980. Relations between the inactivation of sodium channels and the immobilization of gating charge in frog myelinated nerve. J. Physiol. 299:573–603
    [Google Scholar]
  88. 88.
    Oliver D, Lien CC, Soom M, Baukrowitz T, Jonas P, Fakler B 2004. Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids. Science 304:265–70
    [Google Scholar]
  89. 89.
    Palm D, Uzoni A, Simon F, Fischer M, Coogan A et al. 2021. Evolutionary conservations, changes of circadian rhythms and their effect on circadian disturbances and therapeutic approaches. Neurosci. Biobehav. Rev. 128:21–34
    [Google Scholar]
  90. 90.
    Pan X, Li Z, Huang X, Huang G, Gao S et al. 2019. Molecular basis for pore blockade of human Na+ channel Nav1.2 by the μ-conotoxin KIIIA. Science 363:1309–13
    [Google Scholar]
  91. 91.
    Pan X, Li Z, Zhou Q, Shen H, Wu K et al. 2018. Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1. Science 362:eaau2486
    [Google Scholar]
  92. 92.
    Papazian DM, Schwarz TL, Tempel BL, Jan YN, Jan LY 1987. Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila. Science 237:749–53
    [Google Scholar]
  93. 93.
    Patton DE, West JW, Catterall WA, Goldin AL. 1992. Amino acid residues required for fast Na+-channel inactivation: charge neutralizations and deletions in the III-IV linker. PNAS 89:10905–9
    [Google Scholar]
  94. 94.
    Pau V, Zhou Y, Ramu Y, Xu Y, Lu Z. 2017. Crystal structure of an inactivated mutant mammalian voltage-gated K+ channel. Nat. Struct. Mol. Biol. 24:857–65
    [Google Scholar]
  95. 95.
    Pau VP, Abarca-Heidemann K, Rothberg BS. 2010. Allosteric mechanism of Ca2+ activation and H+-inhibited gating of the MthK K+ channel. J. Gen. Physiol. 135:509–26
    [Google Scholar]
  96. 96.
    Peri R, Wible BA, Brown AM. 2001. Mutations in the Kvβ2 binding site for NADPH and their effects on Kv1.4. J. Biol. Chem. 276:738–41
    [Google Scholar]
  97. 97.
    Pfaffinger PJ. 2013. A conserved pre-block interaction motif regulates potassium channel activation and N-type inactivation. PLOS ONE 8:e79891
    [Google Scholar]
  98. 98.
    Pitts GR, Ohta H, McMahon DG. 2006. Daily rhythmicity of large-conductance Ca2+-activated K+ currents in suprachiasmatic nucleus neurons. Brain Res. 1071:54–62
    [Google Scholar]
  99. 99.
    Pongs O, Schwarz JR. 2010. Ancillary subunits associated with voltage-dependent K+ channels. Physiol. Rev. 90:755–96
    [Google Scholar]
  100. 100.
    Posson DJ, Rusinova R, Andersen OS, Nimigean CM. 2015. Calcium ions open a selectivity filter gate during activation of the MthK potassium channel. Nat. Commun. 6:8342
    [Google Scholar]
  101. 101.
    Prince-Carter A, Pfaffinger PJ 2009. Multiple intermediate states precede pore block during N-type inactivation of a voltage-gated potassium channel. J. Gen. Physiol. 134:15–34
    [Google Scholar]
  102. 102.
    Rasmusson RL, Morales MJ, Wang S, Liu S, Campbell DL et al. 1998. Inactivation of voltage-gated cardiac K+ channels. Circ. Res. 82:739–50
    [Google Scholar]
  103. 103.
    Ren D, Navarro B, Xu H, Yue L, Shi Q, Clapham DE. 2001. A prokaryotic voltage-gated sodium channel. Science 294:2372–75
    [Google Scholar]
  104. 104.
    Rettig J, Heinemann SH, Wunder F, Lorra C, Parcej DN et al. 1994. Inactivation properties of voltage-gated K+ channels altered by presence of β-subunit. Nature 369:289–94
    [Google Scholar]
  105. 105.
    Ritter DM, Ho C, O'Leary ME, Covarrubias M 2012. Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons. J. Physiol. 590:145–61
    [Google Scholar]
  106. 106.
    Ritter DM, Zemel BM, Lepore AC, Covarrubias M. 2015. Kv3.4 channel function and dysfunction in nociceptors. Channels 9:209–17
    [Google Scholar]
  107. 107.
    Roeper J, Lorra C, Pongs O. 1997. Frequency-dependent inactivation of mammalian A-type K+ channel KV1.4 regulated by Ca2+/calmodulin-dependent protein kinase. J. Neurosci. 17:3379–91
    [Google Scholar]
  108. 108.
    Ruppersberg JP, Stocker M, Pongs O, Heinemann SH, Frank R, Koenen M. 1991. Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation. Nature 352:711–14
    [Google Scholar]
  109. 109.
    Schott MK, Antz C, Frank R, Ruppersberg JP, Kalbitzer HR. 1998. Structure of the inactivating gate from the Shaker voltage gated K+ channel analyzed by NMR spectroscopy. Eur. Biophys. J. 27:99–104
    [Google Scholar]
  110. 110.
    Schwarz TL, Tempel BL, Papazian DM, Jan YN, Jan LY 1988. Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila. Nature 331:137–42
    [Google Scholar]
  111. 111.
    Shen H, Liu D, Wu K, Lei J, Yan N 2019. Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins. Science 363:1303–8
    [Google Scholar]
  112. 112.
    Sokolova O, Kolmakova-Partensky L, Grigorieff N. 2001. Three-dimensional structure of a voltage-gated potassium channel at 2.5 nm resolution. Structure 9:215–20
    [Google Scholar]
  113. 113.
    Stuhmer W, Conti F, Suzuki H, Wang XD, Noda M et al. 1989. Structural parts involved in activation and inactivation of the sodium channel. Nature 339:597–603
    [Google Scholar]
  114. 114.
    Takeda M, Tanimoto T, Nasu M, Matsumoto S. 2008. Temporomandibular joint inflammation decreases the voltage-gated K+ channel subtype 1.4-immunoreactivity of trigeminal ganglion neurons in rats. Eur. J. Pain 12:189–95
    [Google Scholar]
  115. 115.
    Tan XF, Bae C, Stix R, Fernandez-Marino AI, Huffer K et al. 2022. Structure of the Shaker Kv channel and mechanism of slow C-type inactivation. Sci. Adv. 8:eabm7814
    [Google Scholar]
  116. 116.
    Tanouye MA, Kamb CA, Iverson LE, Salkoff L. 1986. Genetics and molecular biology of ionic channels in Drosophila. Annu. Rev. Neurosci. 9:255–76
    [Google Scholar]
  117. 117.
    Tao X, Hite RK, MacKinnon R. 2017. Cryo-EM structure of the open high-conductance Ca2+-activated K+ channel. Nature 541:46–51
    [Google Scholar]
  118. 118.
    Tao X, MacKinnon R 2019. Molecular structures of the human Slo1 K+ channel in complex with β4. eLife 8:e51409
    [Google Scholar]
  119. 119.
    Tarrant AM, Reitzel AM. 2013. Introduction to the symposium—keeping time during evolution: conservation and innovation of the circadian clock. Integr. Comp. Biol. 53:89–92
    [Google Scholar]
  120. 120.
    Tempel BL, Papazian DM, Schwarz TL, Jan YN, Jan LY 1987. Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. Science 237:770–75
    [Google Scholar]
  121. 121.
    Timpe LC, Jan YN, Jan LY 1988. Four cDNA clones from the Shaker locus of Drosophila induce kinetically distinct A-type potassium currents in Xenopus oocytes. Neuron 1:659–67
    [Google Scholar]
  122. 122.
    Timpe LC, Schwarz TL, Tempel BL, Papazian DM, Jan YN, Jan LY 1988. Expression of functional potassium channels from Shaker cDNA in Xenopus oocytes. Nature 331:143–45
    [Google Scholar]
  123. 123.
    Toro L, Stefani E, Latorre R 1992. Internal blockade of a Ca2+-activated K+ channel by Shaker B inactivating “ball” peptide. Neuron 9:237–45
    [Google Scholar]
  124. 124.
    Uebele VN, Lagrutta A, Wade T, Figueroa DJ, Liu Y et al. 2000. Cloning and functional expression of two families of β-subunits of the large conductance calcium-activated K+ channel. J. Biol. Chem. 275:23211–18
    [Google Scholar]
  125. 125.
    Valiyaveetil FI. 2017. A glimpse into the C-type-inactivated state for a potassium channel. Nat. Struct. Mol. Biol. 24:787–88
    [Google Scholar]
  126. 126.
    Vassilev P, Scheuer T, Catterall WA. 1989. Inhibition of inactivation of single sodium channels by a site-directed antibody. PNAS 86:8147–51
    [Google Scholar]
  127. 127.
    Vassilev PM, Scheuer T, Catterall WA. 1988. Identification of an intracellular peptide segment involved in sodium channel inactivation. Science 241:1658–61
    [Google Scholar]
  128. 128.
    Vydyanathan A, Wu ZZ, Chen SR, Pan HL. 2005. A-type voltage-gated K+ currents influence firing properties of isolectin B4-positive but not isolectin B4-negative primary sensory neurons. J. Neurophysiol. 93:3401–9
    [Google Scholar]
  129. 129.
    Wallner M, Meera P, Toro L. 1999. Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane β-subunit homolog. PNAS 96:4137–42
    [Google Scholar]
  130. 130.
    Wang YW, Ding JP, Xia XM, Lingle CJ. 2002. Consequences of the stoichiometry of Slo1 α and auxiliary β subunits on functional properties of large-conductance Ca2+-activated K+ channels. J. Neurosci. 22:1550–61
    [Google Scholar]
  131. 131.
    Waxman SG, Zamponi GW. 2014. Regulating excitability of peripheral afferents: emerging ion channel targets. Nat. Neurosci. 17:153–63
    [Google Scholar]
  132. 132.
    Welsh DK, Takahashi JS, Kay SA. 2010. Suprachiasmatic nucleus: cell autonomy and network properties. Annu. Rev. Physiol. 72:551–77
    [Google Scholar]
  133. 133.
    Weng J, Cao Y, Moss N, Zhou M. 2006. Modulation of voltage-dependent Shaker family potassium channels by an aldo-keto reductase. J. Biol. Chem. 281:15194–200
    [Google Scholar]
  134. 134.
    West JW, Patton DE, Scheuer T, Wang Y, Goldin AL, Catterall WA. 1992. A cluster of hydrophobic amino acid residues required for fast Na+-channel inactivation. PNAS 89:10910–14
    [Google Scholar]
  135. 135.
    Whitt JP, Montgomery JR, Meredith AL. 2016. BK channel inactivation gates daytime excitability in the circadian clock. Nat. Commun. 7:10837
    [Google Scholar]
  136. 136.
    Wissmann R, Bildl W, Oliver D, Beyermann M, Kalbitzer HR et al. 2003. Solution structure and function of the “tandem inactivation domain” of the neuronal A-type potassium channel Kv1.4. J. Biol. Chem. 278:16142–50
    [Google Scholar]
  137. 137.
    Xia XM, Ding JP, Lingle CJ. 2003. Inactivation of BK channels by the NH2 terminus of the β2 auxiliary subunit: an essential role of a terminal peptide segment of three hydrophobic residues. J. Gen. Physiol. 121:125–48
    [Google Scholar]
  138. 138.
    Xu Y, McDermott AE. 2019. Inactivation in the potassium channel KcsA. J. Struct. Biol. X 3:100009
    [Google Scholar]
  139. 139.
    Yan J, Li Q, Aldrich RW 2016. Closed state-coupled C-type inactivation in BK channels. PNAS 113:6991–96
    [Google Scholar]
  140. 140.
    Yang H, Zhang G, Cui J. 2015. BK channels: multiple sensors, one activation gate. Front. Physiol. 6:29
    [Google Scholar]
  141. 141.
    Ye S, Li Y, Chen L, Jiang Y 2006. Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of K+ channels. Cell 126:1161–73
    [Google Scholar]
  142. 142.
    Yeh JZ, Narahashi T. 1977. Kinetic analysis of pancuronium interaction with sodium channels in squid axon membranes. J. Gen. Physiol. 69:293–323
    [Google Scholar]
  143. 143.
    Yellen G. 1998. The moving parts of voltage-gated ion channels. Q. Rev. Biophys. 31:239–95
    [Google Scholar]
  144. 144.
    Zadek B, Nimigean CM. 2006. Calcium-dependent gating of MthK, a prokaryotic potassium channel. J. Gen. Physiol. 127:673–85
    [Google Scholar]
  145. 145.
    Zagotta WN, Hoshi T, Aldrich RW. 1989. Gating of single Shaker potassium channels in Drosophila muscle and in Xenopus oocytes injected with Shaker mRNA. PNAS 86:7243–47
    [Google Scholar]
  146. 146.
    Zagotta WN, Hoshi T, Aldrich RW. 1990. Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB. Science 250:568–71
    [Google Scholar]
  147. 147.
    Zemel BM, Muqeem T, Brown EV, Goulao M, Urban MW et al. 2017. Calcineurin dysregulation underlies spinal cord injury-induced K+ channel dysfunction in DRG neurons. J. Neurosci. 37:8256–72
    [Google Scholar]
  148. 148.
    Zemel BM, Ritter DM, Covarrubias M, Muqeem T. 2018. A-type KV channels in dorsal root ganglion neurons: diversity, function, and dysfunction. Front. Mol. Neurosci. 11:253
    [Google Scholar]
  149. 149.
    Zhang J, Shi Y, Fan J, Chen H, Xia Z et al. 2022. N-type fast inactivation of a eukaryotic voltage-gated sodium channel. Nat. Commun. 13:2713
    [Google Scholar]
  150. 150.
    Zhou M, Morais-Cabral JH, Mann S, MacKinnon R. 2001. Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. Nature 411:657–61
    [Google Scholar]
  151. 151.
    Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R. 2001. Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 Å resolution. Nature 414:43–48
    [Google Scholar]
/content/journals/10.1146/annurev-biophys-100322-072921
Loading
/content/journals/10.1146/annurev-biophys-100322-072921
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error