1932

Abstract

Ca2+- and voltage-gated K+ channels of large conductance (BK channels) are expressed in a diverse variety of both excitable and inexcitable cells, with functional properties presumably uniquely calibrated for the cells in which they are found. Although some diversity in BK channel function, localization, and regulation apparently arises from cell-specific alternative splice variants of the single pore–forming α subunit (, , ) gene, two families of regulatory subunits, β and γ, define BK channels that span a diverse range of functional properties. We are just beginning to unravel the cell-specific, physiological roles served by BK channels of different subunit composition.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-022516-034038
2019-02-10
2024-06-20
Loading full text...

Full text loading...

/deliver/fulltext/physiol/81/1/annurev-physiol-022516-034038.html?itemId=/content/journals/10.1146/annurev-physiol-022516-034038&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Elkins T, Ganetzky B, Wu CF 1986. A Drosophila mutation that eliminates a calcium-dependent potassium current. PNAS 83:8415–19
    [Google Scholar]
  2. 2.
    Adelman JP, Shen KZ, Kavanaugh MP, Warren RA, Wu YN et al. 1992. Calcium-activated potassium channels expressed from cloned complementary DNAs. Neuron 9:209–16
    [Google Scholar]
  3. 3.
    Butler A, Tsunoda S, McCobb DP, Wei A, Salkoff L 1993. mSlo, a complex mouse gene encoding “maxi” calcium-activated potassium channels. Science 261:221–24
    [Google Scholar]
  4. 4.
    Kimm T, Khaliq ZM, Bean BP 2015. Differential regulation of action potential shape and burst-frequency firing by BK and Kv2 channels in substantia nigra dopaminergic neurons. J. Neurosci. 35:16404–17
    [Google Scholar]
  5. 5.
    Cheron G, Sausbier M, Sausbier U, Neuhuber W, Ruth P et al. 2009. BK channels control cerebellar Purkinje and Golgi cell rhythmicity in vivo. PLOS ONE 4:e7991
    [Google Scholar]
  6. 6.
    Matthews EA, Weible AP, Shah S, Disterhoft JF 2008. The BK-mediated fAHP is modulated by learning a hippocampus-dependent task. PNAS 105:15154–59
    [Google Scholar]
  7. 7.
    Solaro CR, Prakriya M, Ding JP, Lingle CJ 1995. Inactivating and noninactivating Ca2+- and voltage-dependent K+ current in rat adrenal chromaffin cells. J. Neurosci. 15:6110–23
    [Google Scholar]
  8. 8.
    Duncan PJ, Shipston MJ 2016. BK channels and the control of the pituitary. Int. Rev. Neurobiol. 128:343–68
    [Google Scholar]
  9. 9.
    Hayashi Y, Morinaga S, Zhang J, Satoh Y, Meredith AL et al. 2016. BK channels in microglia are required for morphine-induced hyperalgesia. Nat. Commun. 7:11697
    [Google Scholar]
  10. 10.
    Pallotta BS, Magleby KL, Barrett JN 1981. Single channel recordings of Ca2+-activated K+ currents in rat muscle cell culture. Nature 293:471–74
    [Google Scholar]
  11. 11.
    Giangiacomo KM, Garcia-Calvo M, Knaus HG, Mullmann TJ, Garcia ML, McManus O 1995. Functional reconstitution of the large-conductance, calcium-activated potassium channel purified from bovine aortic smooth muscle. Biochemistry 34:15849–62
    [Google Scholar]
  12. 12.
    Scornik FS, Codina J, Birnbaumer L, Toro L 1993. Modulation of coronary smooth muscle KCa channels by Gs alpha independent of phosphorylation by protein kinase A. Am. J. Physiol. 265:H1460–65
    [Google Scholar]
  13. 13.
    Semenov I, Wang B, Herlihy JT, Brenner R 2006. BK channel β1-subunit regulation of calcium handling and constriction in tracheal smooth muscle. Am. J. Physiol. Lung Cell. Mol. Physiol. 291:L802–10
    [Google Scholar]
  14. 14.
    Pacha J, Frindt G, Sackin H, Palmer LG 1991. Apical maxi K channels in intercalated cells of CCT. Am. J. Physiol. 261:F696–705
    [Google Scholar]
  15. 15.
    Grimm PR, Sansom SC 2007. BK channels in the kidney. Curr. Opin. Nephrol. Hypertens. 16:430–36
    [Google Scholar]
  16. 16.
    Palmer LG, Frindt G 2007. High-conductance K channels in intercalated cells of the rat distal nephron. Am. J. Physiol. Renal Physiol. 292:F966–73
    [Google Scholar]
  17. 17.
    Klaerke DA, Wiener H, Zeuthen T, Jorgensen PL 1993. Ca2+ activation and pH dependence of a maxi K+ channel from rabbit distal colon epithelium. J. Membr. Biol. 136:9–21
    [Google Scholar]
  18. 18.
    Sohma Y, Harris A, Wardle C, Gray M, Argent B 1994. Maxi K+ channels on human vas deferens epithelial cells. J. Membr. Biol. 141:69–82
    [Google Scholar]
  19. 19.
    Manzanares D, Gonzalez C, Ivonnet P, Chen RS, Valencia-Gattas M et al. 2011. Functional apical large conductance, Ca2+-activated, and voltage-dependent K+ channels are required for maintenance of airway surface liquid volume. J. Biol. Chem. 286:19830–39
    [Google Scholar]
  20. 20.
    Yang C, Gonzalez-Perez V, Mukaibo T, Melvin JE, Xia XM, Lingle CJ 2017. Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells. PNAS 114:E3739–47
    [Google Scholar]
  21. 21.
    Li B, Jie W, Huang L, Wei P, Li S et al. 2014. Nuclear BK channels regulate gene expression via the control of nuclear calcium signaling. Nat. Neurosci. 17:1055–63
    [Google Scholar]
  22. 22.
    Singh H, Lu R, Bopassa JC, Meredith AL, Stefani E, Toro L 2013. MitoBKCa is encoded by the Kcnma1 gene, and a splicing sequence defines its mitochondrial location. PNAS 110:10836–41
    [Google Scholar]
  23. 23.
    Cao Q, Zhong XZ, Zou Y, Zhang Z, Toro L, Dong XP 2015. BK channels alleviate lysosomal storage diseases by providing positive feedback regulation of lysosomal Ca2+ release. Dev. Cell 33:427–41
    [Google Scholar]
  24. 24.
    Saito M, Nelson C, Salkoff L, Lingle CJ 1997. A cysteine-rich domain defined by a novel exon in a Slo variant in rat adrenal chromaffin cells and PC12 cells. J. Biol. Chem. 272:11710–7
    [Google Scholar]
  25. 25.
    Tseng-Crank J, Foster CD, Krause JD, Mertz R, Godinot N et al. 1994. Cloning, expression, and distribution of functionally distinct Ca2+-activated K+ channel isoforms from human brain. Neuron 13:1315–30
    [Google Scholar]
  26. 26.
    Zarei MM, Zhu N, Alioua A, Eghbali M, Stefani E, Toro L 2001. A novel MaxiK splice variant exhibits dominant-negative properties for surface expression. J. Biol. Chem. 276:16232–39
    [Google Scholar]
  27. 27.
    Soom M, Gessner G, Heuer H, Hoshi T, Heinemann SH 2008. A mutually exclusive alternative exon of slo1 codes for a neuronal BK channel with altered function. Channels 2:278–82
    [Google Scholar]
  28. 28.
    Ling S, Woronuk G, Sy L, Lev S, Braun AP 2000. Enhanced activity of a large conductance, calcium-sensitive K+ channel in the presence of Src tyrosine kinase. J. Biol. Chem. 275:30683–89
    [Google Scholar]
  29. 29.
    Shipston MJ, Tian L 2016. Posttranscriptional and posttranslational regulation of BK channels. Int. Rev. Neurobiol. 128:91–126
    [Google Scholar]
  30. 30.
    Zhou X, Wulfsen I, Korth M, McClafferty H, Lukowski R et al. 2012. Palmitoylation and membrane association of the stress axis regulated insert (STREX) controls BK channel regulation by protein kinase C. J. Biol. Chem. 287:32161–71
    [Google Scholar]
  31. 31.
    Shelley C, Whitt JP, Montgomery JR, Meredith AL 2013. Phosphorylation of a constitutive serine inhibits BK channel variants containing the alternate exon “SRKR. .” J. Gen. Physiol. 142:585–98
    [Google Scholar]
  32. 32.
    Horrigan F, Aldrich R 2002. Coupling between voltage-sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels. J. Gen. Physiol. 120:267–305
    [Google Scholar]
  33. 33.
    Cox D, Aldrich R 2000. Role of the β1 subunit in large-conductance Ca2+-activated K+ channel gating energetics: mechanisms of enhanced Ca2+ sensitivity. J. Gen. Physiol. 116:411–32
    [Google Scholar]
  34. 34.
    Yan J, Aldrich RW 2010. LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium. Nature 466:513–16
    [Google Scholar]
  35. 35.
    Hoshi T, Pantazis A, Olcese R 2013. Transduction of voltage and Ca2+ signals by Slo1 BK channels. Physiology 28:172–89
    [Google Scholar]
  36. 36.
    Geng Y, Magleby KL 2014. Single-channel kinetics of BK (Slo1) channels. Front. Physiol. 5:532
    [Google Scholar]
  37. 37.
    Yang H, Zhang G, Cui J 2015. BK channels: multiple sensors, one activation gate. Front. Physiol. 6:29
    [Google Scholar]
  38. 38.
    Pantazis A, Olcese R 2016. Biophysics of BK channel gating. Int. Rev. Neurobiol. 128:1–49
    [Google Scholar]
  39. 39.
    Latorre R, Castillo K, Carrasquel-Ursulaez W, Sepulveda RV, Gonzalez-Nilo F et al. 2017. Molecular determinants of BK channel functional diversity and functioning. Physiol. Rev. 97:39–87
    [Google Scholar]
  40. 40.
    Zhou Y, Yang H, Cui J, Lingle CJ 2017. Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel. J. Gen. Physiol. 149:985–1007
    [Google Scholar]
  41. 41.
    Contreras GF, Neely A, Alvarez O, Gonzalez C, Latorre R 2012. Modulation of BK channel voltage gating by different auxiliary β subunits. PNAS 109:18991–96
    [Google Scholar]
  42. 42.
    Rothberg BS. 2012. The BK channel: a vital link between cellular calcium and electrical signaling. Protein Cell 3:883–92
    [Google Scholar]
  43. 43.
    Torres YP, Granados ST, Latorre R 2014. Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits. Front. Physiol. 5:383
    [Google Scholar]
  44. 44.
    Zhang J, Yan J 2014. Regulation of BK channels by auxiliary γ subunits. Front. Physiol. 5:401
    [Google Scholar]
  45. 45.
    Krishnamoorthy-Natarajan G, Koide M 2016. BK channels in the vascular system. Int. Rev. Neurobiol. 128:401–38
    [Google Scholar]
  46. 46.
    Contreras GF, Castillo K, Enrique N, Carrasquel-Ursulaez W, Castillo JP et al. 2013. A BK (Slo1) channel journey from molecule to physiology. Channels 7:442–58
    [Google Scholar]
  47. 47.
    Meech RW. 1978. Calcium-dependent potassium activation in nervous tissues. Annu. Rev. Biophys. Bioeng. 7:1–18
    [Google Scholar]
  48. 48.
    Eckert R, Tillotson D 1978. Potassium activation associated with intraneuronal free calcium. Science 200:437–39
    [Google Scholar]
  49. 49.
    Barrett JN, Magleby KL, Pallotta BS 1982. Properties of single calcium-activated potassium channels in cultured rat muscle. J. Physiol. 331:211–30
    [Google Scholar]
  50. 50.
    Marty A. 1981. Ca-dependent K channels with large unitary conductance in chromaffin cell membranes. Nature 291:497–500
    [Google Scholar]
  51. 51.
    Miller C, Moczydlowski E, Latorre R, Phillips M 1985. Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle. Nature 313:316–18
    [Google Scholar]
  52. 52.
    Galvez A, Gimenez-Gallego G, Reuben JP, Roy-Contancin L, Feigenbaum P et al. 1990. Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus. J. Biol. Chem 265:11083–90
    [Google Scholar]
  53. 53.
    Atkinson NS, Robertson GA, Ganetzky B 1991. A component of calcium-activated potassium channels encoded by the Drosophila slo locus. Science 253:551–55
    [Google Scholar]
  54. 54.
    Pallanck L, Ganetzky B 1994. Cloning and characterization of human and mouse homologs of the Drosophila calcium-activated potassium channel gene, slowpoke. Hum. Mol. Genet. 3:1239–43
    [Google Scholar]
  55. 55.
    Wu Y, Yang Y, Ye S, Jiang Y 2010. Structure of the gating ring from the human large-conductance Ca2+-gated K+ channel. Nature 466:393–97
    [Google Scholar]
  56. 56.
    Yuan P, Leonetti MD, Pico AR, Hsiung Y, MacKinnon R 2010. Structure of the human BK channel Ca2+-activation apparatus at 3.0 Å resolution. Science 329:182–86
    [Google Scholar]
  57. 57.
    Yuan P, Leonetti MD, Hsiung Y, MacKinnon R 2012. Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel. Nature 481:94–97
    [Google Scholar]
  58. 58.
    Garcia-Calvo M, Vazquez J, Smith M, Kaczorowski GJ, Garcia ML 1991. Characterization of the solubilized charybdotoxin receptor from bovine aortic smooth muscle. Biochemistry 30:11157–64
    [Google Scholar]
  59. 59.
    Garcia-Calvo M, Knaus HG, McManus OB, Giangiacomo KM, Kaczorowski GJ, Garcia ML 1994. Purification and reconstitution of the high-conductance, calcium-activated potassium channel from tracheal smooth muscle. J. Biol. Chem. 269:676–82
    [Google Scholar]
  60. 60.
    Knaus HG, Folander K, Garcia-Calvo M, Garcia ML, Kaczorowski GJ et al. 1994. Primary sequence and immunological characterization of beta-subunit of high conductance Ca2+-activated K+ channel from smooth muscle. J. Biol. Chem. 269:17274–78
    [Google Scholar]
  61. 61.
    McManus OB, Helms LM, Pallanck L, Ganetzky B, Swanson R, Leonard RJ 1995. Functional role of the β subunit of high conductance calcium-activated potassium channels. Neuron 14:645–50
    [Google Scholar]
  62. 62.
    McManus OB, Harris GH, Giangiacomo KM, Feigenbaum P, Reuben JP et al. 1993. An activator of calcium-dependent potassium channels isolated from a medicinal herb. Biochemistry 32:6128–33
    [Google Scholar]
  63. 63.
    Zbicz KL, Weight FF 1985. Transient voltage and calcium-dependent outward currents in hippocampal CA3 pyramidal neurons. J. Neurophysiol. 53:1038–58
    [Google Scholar]
  64. 64.
    Ikemoto Y, Ono K, Yoshida A, Akaike N 1989. Delayed activation of large-conductance Ca2+-activated K channels in hippocampal neurons of the rat. Biophys. J. 56:207–12
    [Google Scholar]
  65. 65.
    Solaro CR, Lingle CJ 1992. Trypsin-sensitive, rapid inactivation of a calcium-activated potassium channel. Science 257:1694–98
    [Google Scholar]
  66. 66.
    Li ZW, Ding JP, Kalyanaraman V, Lingle CJ 1999. RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels. J. Neurophysiol. 81:611–24
    [Google Scholar]
  67. 67.
    Solaro CR, Ding JP, Li ZW, Lingle CJ 1997. The cytosolic inactivation domains of BKi channels in rat chromaffin cells do not behave like simple, open-channel blockers. Biophys. J. 73:819–30
    [Google Scholar]
  68. 68.
    Reinhart PH, Chung S, Levitan IB 1989. A family of calcium-dependent potassium channels from rat brain. Neuron 2:1031–41
    [Google Scholar]
  69. 69.
    Reinhart PH, Chung S, Martin BL, Brautigan DL, Levitan IB 1991. Modulation of calcium-activated potassium channels from rat brain by protein kinase A and phosphatase 2A. J. Neurosci. 11:1627–35
    [Google Scholar]
  70. 70.
    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]
  71. 71.
    Meera P, Wallner M, Toro L 2000. A neuronal β subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin. PNAS 97:5562–67
    [Google Scholar]
  72. 72.
    Xia X-M, Ding JP, Lingle CJ 1999. Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells. J. Neurosci. 19:5255–64
    [Google Scholar]
  73. 73.
    Xia X-M, Ding J-P, Zeng X-H, Duan K-L, Lingle CJ 2000. Rectification and rapid activation at low Ca2+ of Ca2+-activated, voltage-dependent BK currents: consequences of rapid inactivation by a novel β subunit. J. Neurosci. 20:4890–903
    [Google Scholar]
  74. 74.
    Brenner R, Jegla TJ, Wickenden A, Liu Y, Aldrich RW 2000. Cloning and functional characterization of novel large conductance calcium-activated potassium channel β subunits, hKCNMB3 and hKCNMB4. J. Biol. Chem. 275:6453–61
    [Google Scholar]
  75. 75.
    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]
  76. 76.
    Weiger TM, Holmqvist MH, Levitan IB, Clark FT, Sprague S et al. 2000. A novel nervous system β subunit that downregulates human large conductance calcium-dependent potassium channels. J. Neurosci. 20:3563–70
    [Google Scholar]
  77. 77.
    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]
  78. 78.
    Martinez-Espinosa P, Yang C, Gonzalez-Perez V, Xia XM, Lingle CJ 2014. Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity. J. Gen. Physiol. 144:275–95
    [Google Scholar]
  79. 79.
    Zeng X, Xia XM, Lingle CJ 2008. Species-specific differences among KCNMB3 BK β3 auxiliary subunits: some β3 variants may be primate-specific subunits. J. Gen. Physiol. 132:115–29
    [Google Scholar]
  80. 80.
    Zeng X-H, Xia XM, Lingle CJ 2007. BK channels with β3a subunits generate use-dependent slow afterhyperpolarizing currents by an inactivation-coupled mechanism. J. Neurosci. 27:4707–15
    [Google Scholar]
  81. 81.
    Nimigean CM, Magleby KL 2000. Functional coupling of the β1 subunit to the large conductance Ca2+-activated K+ channel in the absence of Ca2+. Increased Ca2+ sensitivity from a Ca2+-independent mechanism. J. Gen. Physiol. 115:719–36
    [Google Scholar]
  82. 82.
    Orio P, Latorre R 2005. Differential effects of β1 and β2 subunits on BK channel activity. J. Gen. Physiol. 125:395–411
    [Google Scholar]
  83. 83.
    Ding J, Lingle C 2002. Steady-state and closed-state inactivation properties of inactivating BK channels. Biophys. J. 82:2448–65
    [Google Scholar]
  84. 84.
    Zeng X-H, Xia X-M, Lingle CJ 2003. Redox-sensitive extracellular gates formed by auxiliary β subunits of calcium-activated potassium channels. Nat. Struct. Biol. 10:448–54
    [Google Scholar]
  85. 85.
    Chen M, Gan G, Wu Y, Wang L, Ding J 2008. Lysine-rich extracellular rings formed by hβ2 subunits confer the outward rectification of BK channels. PLOS ONE 3:e2114
    [Google Scholar]
  86. 86.
    Gonzalez-Perez V, Zeng X-H, Henzler-Wildman K, Lingle CJ 2012. Stereospecific binding of a disordered peptide segment mediates BK channel inactivation. Nature 485:133–36
    [Google Scholar]
  87. 87.
    Lingle CJ, Zeng X-H, Ding J-P, Xia X-M 2001. Inactivation of BK channels mediated by the NH2 terminus of the β3b auxiliary subunit involves a two-step mechanism. J. Gen. Physiol 117:583–605
    [Google Scholar]
  88. 88.
    Wang B, Rothberg BS, Brenner R 2006. Mechanism of β4 subunit modulation of BK channels. J. Gen. Physiol. 127:449–65
    [Google Scholar]
  89. 89.
    Wang Y-W, Ding JP, Xia X-M, Lingle CJ 2002. Consequences of the stoichiometry of Slo1 α and auxiliary β subunits on functional properties of BK-type Ca2+-activated K+ channels. J. Neurosci. 22:1550–61
    [Google Scholar]
  90. 90.
    Ding JP, Li ZW, Lingle CJ 1998. Inactivating BK channels in rat chromaffin cells may arise from heteromultimeric assembly of distinct inactivation-competent and noninactivating subunits. Biophys. J. 74:268–89
    [Google Scholar]
  91. 91.
    Kuntamallappanavar G, Bisen S, Bukiya AN, Dopico AM 2017. Differential distribution and functional impact of BK channel beta1 subunits across mesenteric, coronary, and different cerebral arteries of the rat. Pflügers Arch 469:263–77
    [Google Scholar]
  92. 92.
    Wang B, Jaffe DB, Brenner R 2014. Current understanding of iberiotoxin-resistant BK channels in the nervous system. Front. Physiol. 5:382
    [Google Scholar]
  93. 93.
    MacKinnon R. 1991. Determination of the subunit stoichiometry of a voltage-activated potassium channel. Nature 350:232–35
    [Google Scholar]
  94. 94.
    Gessner G, Schönherr K, Soom M, Hansel A, Asim M et al. 2005. BKCa channels activating at resting potential without calcium in LNCaP prostate cancer cells. J. Membr. Biol. 208:229–40
    [Google Scholar]
  95. 95.
    Ransom CB, Liu X, Sontheimer H 2002. BK channels in human glioma cells have enhanced calcium sensitivity. Glia 38:281–91
    [Google Scholar]
  96. 96.
    Marty A, Tan YP, Trautmann A 1984. Three types of calcium-dependent channel in rat lacrimal glands. J. Physiol. 357:293–325
    [Google Scholar]
  97. 97.
    Yan J, Aldrich RW 2012. BK potassium channel modulation by leucine-rich repeat-containing proteins. PNAS 109:7917–22
    [Google Scholar]
  98. 98.
    Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S et al. 2007. The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genom 8:320–43
    [Google Scholar]
  99. 99.
    Kim HM, Oh SC, Lim KJ, Kasamatsu J, Heo JY et al. 2007. Structural diversity of the hagfish variable lymphocyte receptors. J. Biol. Chem. 282:6726–32
    [Google Scholar]
  100. 100.
    Gonzalez-Perez V, Xia XM, Lingle CJ 2014. Functional regulation of BK potassium channels by γ1 auxiliary subunits. PNAS 111:4868–73
    [Google Scholar]
  101. 101.
    Carrasquel-Ursulaez W, Alvarez O, Bezanilla F, Latorre R 2018. Determination of the stoichiometry between α- and γ1 subunits of the BK channel using LRET. Biophys. J. 114:2493–97
    [Google Scholar]
  102. 102.
    Gonzalez-Perez V, Johny MB, Xia X-M, Lingle CJ 2018. Regulatory γ1 subunits defy symmetry in functional modulation of BK channels. PNAS 115:9923–28
    [Google Scholar]
  103. 103.
    Gonzalez-Perez V, Xia XM, Lingle CJ 2015. Two classes of regulatory subunits coassemble in the same BK channel and independently regulate gating. Nat. Commun. 6:8341
    [Google Scholar]
  104. 104.
    Zakharov SI, Morrow JP, Liu G, Yang L, Marx SO 2005. Activation of the BK (SLO1) potassium channel by mallotoxin. J. Biol. Chem. 280:30882–87
    [Google Scholar]
  105. 105.
    Romanenko VG, Thompson J, Begenisich T 2010. Ca2+-activated K channels in parotid acinar cells: the functional basis for the hyperpolarized activation of BK channels. Channels 4:278–88
    [Google Scholar]
  106. 106.
    Almassy J, Begenisich T 2012. The LRRC26 protein selectively alters the efficacy of BK channel activators. Mol. Pharmacol. 81:21–30
    [Google Scholar]
  107. 107.
    Manzanares D, Srinivasan M, Salathe ST, Ivonnet P, Baumlin N et al. 2014. IFN-γ-mediated reduction of large-conductance, Ca2+-activated, voltage-dependent K+ (BK) channel activity in airway epithelial cells leads to mucociliary dysfunction. Am. J. Physiol. Lung Cell. Mol. Physiol. 306:L453–62
    [Google Scholar]
  108. 108.
    Manzanares D, Krick S, Baumlin N, Dennis JS, Tyrrell J et al. 2015. Airway surface dehydration by transforming growth factor β (TGF-β) in cystic fibrosis is due to decreased function of a voltage-dependent potassium channel and can be rescued by the drug pirfenidone. J. Biol. Chem. 290:25710–16
    [Google Scholar]
  109. 109.
    Navarro B, Kirichok Y, Clapham DE 2007. KSper, a pH-sensitive K+ current that controls sperm membrane potential. PNAS 104:7688–92
    [Google Scholar]
  110. 110.
    Zeng XH, Yang C, Kim ST, Lingle CJ, Xia XM 2011. Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa. PNAS 108:5879–84
    [Google Scholar]
  111. 111.
    Zeng XH, Yang C, Xia XM, Liu M, Lingle CJ 2015. SLO3 auxiliary subunit LRRC52 controls gating of sperm KSPER currents and is critical for normal fertility. PNAS 112:2599–604
    [Google Scholar]
  112. 112.
    Yang C, Zeng XH, Zhou Y, Xia XM, Lingle CJ 2011. LRRC52 (leucine-rich-repeat-containing protein 52), a testis-specific auxiliary subunit of the alkalization-activated Slo3 channel. PNAS 108:19419–24
    [Google Scholar]
  113. 113.
    Zhang YY, Han X, Liu Y, Chen J, Hua L et al. 2018. +mRNA expression of LRRC55 protein (leucine-rich repeat-containing protein 55) in the adult mouse brain. PLOS ONE 13:e0191749
    [Google Scholar]
  114. 114.
    Brenner R, Perez G, Bonev A, Eckman D, Kosek J et al. 2000. Vasoregulation by the β1 subunit of the calcium-activated potassium channel. Nature 407:870–75
    [Google Scholar]
  115. 115.
    Plüger S, Faulhaber J, Furstenau M, Lohn M, Waldschutz R et al. 2000. Mice with disrupted BK channel β1 subunit gene feature abnormal Ca2+ spark/STOC coupling and elevated blood pressure. Circ. Res. 87:E53–60
    [Google Scholar]
  116. 116.
    Semenov I, Wang B, Herlihy JT, Brenner R 2011. BK channel β1 subunits regulate airway contraction secondary to M2 muscarinic acetylcholine receptor mediated depolarization. J. Physiol. 589:1803–17
    [Google Scholar]
  117. 117.
    Petkov GV, Bonev AD, Heppner TJ, Brenner R, Aldrich RW, Nelson MT 2001. β1-Subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle. J. Physiol. 537:443–52
    [Google Scholar]
  118. 118.
    Nelson MT, Cheng H, Rubart M, Santana LF, Bonev AD et al. 1995. Relaxation of arterial smooth muscle by calcium sparks. Science 270:633–37
    [Google Scholar]
  119. 119.
    Jaggar JH, Wellman GC, Heppner TJ, Porter VA, Perez GJ et al. 1998. Ca2+ channels, ryanodine receptors and Ca2+-activated K+ channels: a functional unit for regulating arterial tone. Acta Physiol. Scand. 164:577–87
    [Google Scholar]
  120. 120.
    Wellman GC, Nelson MT 2003. Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-sensitive ion channels. Cell Calcium 34:211–29
    [Google Scholar]
  121. 121.
    ZhuGe R, Tuft RA, Fogarty KE, Bellve K, Fay FS, Walsh JV Jr 1999. The influence of sarcoplasmic reticulum Ca2+ concentration on Ca2+ sparks and spontaneous transient outward currents in single smooth muscle cells. J. Gen. Physiol. 113:215–28
    [Google Scholar]
  122. 122.
    Perez GJ, Bonev AD, Nelson MT 2001. Micromolar Ca2+ from sparks activates Ca2+-sensitive K+ channels in rat cerebral artery smooth muscle. Am. J. Physiol. Cell Physiol. 281:C1769–75
    [Google Scholar]
  123. 123.
    ZhuGe R, Fogarty KE, Tuft RA, Walsh JV Jr 2002. Spontaneous transient outward currents arise from microdomains where BK channels are exposed to a mean Ca2+ concentration on the order of 10 μM during a Ca2+ spark. J. Gen. Physiol. 120:15–27
    [Google Scholar]
  124. 124.
    Xu H, Garver H, Galligan JJ, Fink GD 2011. Large-conductance Ca2+-activated K+ channel β1-subunit knockout mice are not hypertensive. Am. J. Physiol. Heart Circ. Physiol. 300:H476–85
    [Google Scholar]
  125. 125.
    Grimm PR, Irsik DL, Settles DC, Holtzclaw JD, Sansom SC 2009. Hypertension of Kcnmb1−/− is linked to deficient K secretion and aldosteronism. PNAS 106:11800–5
    [Google Scholar]
  126. 126.
    Sausbier M, Arntz C, Bucurenciu I, Zhao H, Zhou XB et al. 2005. Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice. Circulation 112:60–68
    [Google Scholar]
  127. 127.
    Sentí M, Fernández-Fernández JM, Tomás M, Vázquez E, Elosua R et al. 2005. Protective effect of the KCNMB1 E65K genetic polymorphism against diastolic hypertension in aging women and its relevance to cardiovascular risk. Circ. Res. 97:1360–65
    [Google Scholar]
  128. 128.
    Fernández-Fernández JM, Tomás M, Vázquez E, Orio P, Latorre R et al. 2004. Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension. J. Clin. Investig. 113:1032–39
    [Google Scholar]
  129. 129.
    Yang Y, Li PY, Cheng J, Mao L, Wen J et al. 2013. Function of BKCa channels is reduced in human vascular smooth muscle cells from Han Chinese patients with hypertension. Hypertension 61:519–25
    [Google Scholar]
  130. 130.
    Hoshi T, Wissuwa B, Tian Y, Tajima N, Xu R et al. 2013. Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels. PNAS 110:4816–21
    [Google Scholar]
  131. 131.
    Welling PA. 2016. Roles and regulation of renal K channels. Annu. Rev. Physiol. 78:415–35
    [Google Scholar]
  132. 132.
    Guggino SE, Guggino WB, Green N, Sacktor B 1987. Blocking agents of Ca2+-activated K+ channels in cultured medullary thick ascending limb cells. Am. J. Physiol. 252:C128–37
    [Google Scholar]
  133. 133.
    Guggino SE, Guggino WB, Green N, Sacktor B 1987. Ca2+-activated K+ channels in cultured medullary thick ascending limb cells. Am. J. Physiol. 252:C121–27
    [Google Scholar]
  134. 134.
    Frindt G, Palmer LG 1987. Ca-activated K channels in apical membrane of mammalian CCT, and their role in K secretion. Am. J. Physiol. 252:F458–67
    [Google Scholar]
  135. 135.
    Grimm PR, Foutz RM, Brenner R, Sansom SC 2007. Identification and localization of BK-β subunits in the distal nephron of the mouse kidney. Am. J. Physiol. Renal Physiol. 293:F350–9
    [Google Scholar]
  136. 136.
    Taniguchi J, Guggino WB 1989. Membrane stretch: a physiological stimulator of Ca2+-activated K+ channels in thick ascending limb. Am. J. Physiol. 257:F347–52
    [Google Scholar]
  137. 137.
    Hanaoka K, Wright JM, Cheglakov IB, Morita T, Guggino WB 1999. A 59 amino acid insertion increases Ca2+ sensitivity of rbslo1, a Ca2+ -activated K+ channel in renal epithelia. J. Membr. Biol. 172:193–201
    [Google Scholar]
  138. 138.
    Xie J, McCobb DP 1998. Control of alternative splicing of potassium channels by stress hormones. Science 280:443–46
    [Google Scholar]
  139. 139.
    Naruse K, Tang QY, Sokabe M 2009. Stress-Axis Regulated Exon (STREX) in the C terminus of BKCa channels is responsible for the stretch sensitivity. Biochem. Biophys. Res. Commun. 385:634–39
    [Google Scholar]
  140. 140.
    Li Y, Hu H, Tian JB, Zhu MX, O'Neil RG 2017. Dynamic coupling between TRPV4 and Ca2+-activated SK1/3 and IK1 K+ channels plays a critical role in regulating the K+-secretory BK channel in kidney collecting duct cells. Am. J. Physiol. Renal Physiol. 312:F1081–89
    [Google Scholar]
  141. 141.
    Pluznick JL, Wei P, Grimm PR, Sansom SC 2005. BK-β1 subunit: immunolocalization in the mammalian connecting tubule and its role in the kaliuretic response to volume expansion. Am. J. Physiol. Renal Physiol. 288:F846–54
    [Google Scholar]
  142. 142.
    Holtzclaw JD, Grimm PR, Sansom SC 2010. Intercalated cell BK-α/β4 channels modulate sodium and potassium handling during potassium adaptation. J. Am. Soc. Nephrol. 21:634–45
    [Google Scholar]
  143. 143.
    Holtzclaw JD, Grimm PR, Sansom SC 2011. Role of BK channels in hypertension and potassium secretion. Curr. Opin. Nephrol. Hypertens. 20:512–17
    [Google Scholar]
  144. 144.
    Whitt JP, Montgomery JR, Meredith AL 2016. BK channel inactivation gates daytime excitability in the circadian clock. Nat. Commun. 7:10837
    [Google Scholar]
  145. 145.
    Li W, Gao SB, Lv CX, Wu Y, Guo ZH et al. 2007. Characterization of voltage-and Ca2+-activated K+ channels in rat dorsal root ganglion neurons. J. Cell Physiol. 212:348–57
    [Google Scholar]
  146. 146.
    Hicks GA, Marrion NV 1998. Ca2+-dependent inactivation of large conductance Ca2+-activated K+ (BK) channels in rat hippocampal neurones produced by pore block from an associated particle. J. Physiol. 508:Pt. 3721–34
    [Google Scholar]
  147. 147.
    Grimes WN, Li W, Chavez AE, Diamond JS 2009. BK channels modulate pre- and postsynaptic signaling at reciprocal synapses in retina. Nat. Neurosci. 12:585–92
    [Google Scholar]
  148. 148.
    Benton MD, Lewis AH, Bant JS, Raman IM 2013. Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata. J. Neurophysiol. 109:2528–41
    [Google Scholar]
  149. 149.
    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]
  150. 150.
    Clay JR. 2017. Novel description of the large conductance Ca2+-modulated K+ channel current, BK, during an action potential from suprachiasmatic nucleus neurons. Physiol. Rep. 5:e13473
    [Google Scholar]
  151. 151.
    Laerum H, Storm JF 1994. Hippocampal long-term potentiation is not accompanied by presynaptic spike broadening, unlike synaptic potentiation by K+ channel blockers. Brain Res 637:349–55
    [Google Scholar]
  152. 152.
    Shao LR, Halvorsrud R, Borg-Graham L, Storm JF 1999. The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells. J. Physiol. 521:Part 1135–46
    [Google Scholar]
  153. 153.
    Faber ES, Sah P 2003. Ca2+-activated K+ (BK) channel inactivation contributes to spike broadening during repetitive firing in the rat lateral amygdala. J. Physiol. 552:483–97
    [Google Scholar]
  154. 154.
    Lorenz S, Heils A, Kasper JM, Sander T 2007. Allelic association of a truncation mutation of the KCNMB3 gene with idiopathic generalized epilepsy. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B:10–13
    [Google Scholar]
  155. 155.
    Zheng JS, Arnett DK, Parnell LD, Lee YC, Ma Y et al. 2013. Polyunsaturated fatty acids modulate the association between PIK3CA-KCNMB3 genetic variants and insulin resistance. PLOS ONE 8:e67394
    [Google Scholar]
  156. 156.
    Petho Z, Tanner MR, Tajhya RB, Huq R, Laragione T et al. 2016. Different expression of β subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes. Arthritis Res. Ther. 18:103
    [Google Scholar]
  157. 157.
    Brenner R, Chen QH, Vilaythong A, Toney GM, Noebels JL, Aldrich RW 2005. BK channel β4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures. Nat. Neurosci. 8:1752–59
    [Google Scholar]
  158. 158.
    Shruti S, Urban-Ciecko J, Fitzpatrick JA, Brenner R, Bruchez MP, Barth AL 2012. The brain-specific β4 subunit downregulates BK channel cell surface expression. PLOS ONE 7:e33429
    [Google Scholar]
  159. 159.
    Wang B, Bugay V, Ling L, Chuang HH, Jaffe DB, Brenner R 2016. Knockout of the BK β4 subunit promotes a functional coupling of BK channels and ryanodine receptors that mediate a fAHP-induced increase in excitability. J. Neurophysiol. 116:456–65
    [Google Scholar]
  160. 160.
    Jaffe DB, Brenner R 2018. A computational model for how the fast afterhyperpolarization paradoxically increases gain in regularly firing neurons. J. Neurophysiol. 119:1506–20
    [Google Scholar]
  161. 161.
    Jaffe DB, Wang B, Brenner R 2011. Shaping of action potentials by type I and type II large-conductance Ca2+-activated K+ channels. Neuroscience 192:205–18
    [Google Scholar]
  162. 162.
    Nakamoto T, Romanenko VG, Takahashi A, Begenisich T, Melvin JE 2008. Apical maxi-K (KCa1.1) channels mediate K+ secretion by the mouse submandibular exocrine gland. Am. J. Physiol. Cell Physiol. 294:C810–19
    [Google Scholar]
  163. 163.
    Romanenko VG, Nakamoto T, Srivastava A, Begenisich T, Melvin JE 2007. Regulation of membrane potential and fluid secretion by Ca2+-activated K+ channels in mouse submandibular glands. J. Physiol. 581:801–17
    [Google Scholar]
  164. 164.
    Wu RS, Marx SO 2010. The BK potassium channel in the vascular smooth muscle and kidney: α- and β-subunits. Kidney Int 78:963–74
    [Google Scholar]
/content/journals/10.1146/annurev-physiol-022516-034038
Loading
/content/journals/10.1146/annurev-physiol-022516-034038
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