BK Channelopathies and KCNMA1-Linked Disease Models

Literature Cited

1. 1.

   Meredith AL. 2015. Genetic methods for studying ion channel function in physiology and disease. Handbook of Ion Channels MC Trudeau, J Zheng 167–88 Boca Raton, FL: CRC Press
   [Google Scholar]
2. 2.

   Bailey CS, Moldenhauer HJ, Park SM, Keros S, Meredith AL. 2019. KCNMA1-linked channelopathy. J. Gen. Physiol. 151:1173–89
   [Google Scholar]
3. 3.

   Miller JP, Moldenhauer HJ, Keros S, Meredith AL. 2021. An emerging spectrum of variants and clinical features in KCNMA1-linked channelopathy. Channels 15:447–64
   [Google Scholar]
4. 4.

   Liang L, Li X, Moutton S, Schrier Vergano SA, Cogne B et al. 2019. De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes. Hum. Mol. Genet. 28:2937–51
   [Google Scholar]
5. 5.

   Du W, Bautista JF, Yang H, Diez-Sampedro A, You SA et al. 2005. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat. Genet. 37:733–38
   [Google Scholar]
6. 6.

   Hébert B, Pietropaolo S, Même S, Laudier B, Laugeray A et al. 2014. Rescue of fragile X syndrome phenotypes in Fmr1KO mice by a BKCa channel opener molecule. Orphanet J. Rare Dis. 9:124
   [Google Scholar]
7. 7.

   Srinivasan SR, Huang H, Chang WC, Nasburg JA, Nguyen HM et al. 2022. Discovery of novel activators of large-conductance calcium-activated potassium channels for the treatment of cerebellar ataxia. Mol. Pharmacol. 102:438–49
   [Google Scholar]
8. 8.

   Gribkoff VK, Starrett JE Jr., Dworetzky SI, Hewawasam P, Boissard CG et al. 2001. Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels. Nat. Med. 7:471–77
   [Google Scholar]
9. 9.

   Gribkoff VK, Winquist RJ. 2023. Potassium channelopathies associated with epilepsy-related syndromes and directions for therapeutic intervention. Biochem. Pharmacol. 208:115413
   [Google Scholar]
10. 10.

    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]
11. 11.

    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]
12. 12.

    Elkins T, Ganetzky B, Wu CF. 1986. A Drosophila mutation that eliminates a calcium-dependent potassium current. PNAS 83:8415–19
    [Google Scholar]
13. 13.

    McCobb DP, Fowler NL, Featherstone T, Lingle CJ, Saito M et al. 1995. A human calcium-activated potassium channel gene expressed in vascular smooth muscle. Am. J. Physiol. Heart Circ. Physiol. 269:H767–77
    [Google Scholar]
14. 14.

    Xie J, McCobb DP. 1998. Control of alternative splicing of potassium channels by stress hormones. Science 280:443–46
    [Google Scholar]
15. 15.

    Shipston MJ. 2001. Alternative splicing of potassium channels: a dynamic switch of cellular excitability. Trends Cell Biol. 11:353–58
    [Google Scholar]
16. 16.

    Meredith AL. 2023. Alternative splicing. Textbook of Ion Channels 3 J Zheng, MC Trudeau 1–14 Boca Raton, FL: CRC Press
    [Google Scholar]
17. 17.

    Bell TJ, Miyashiro KY, Sul JY, McCullough R, Buckley PT et al. 2008. Cytoplasmic BK_Ca channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons. PNAS 105:1901–6
    [Google Scholar]
18. 18.

    Deng PY, Klyachko VA. 2021. Channelopathies in fragile X syndrome. Nat. Rev. Neurosci. 22:275–89
    [Google Scholar]
19. 19.

    Yuan P, Leonetti MD, Hsiung Y, MacKinnon R. 2011. Open structure of the Ca²⁺ gating ring in the high-conductance Ca²⁺-activated K⁺ channel. Nature 481:94–97
    [Google Scholar]
20. 20.

    Zhang FX, Gadotti VM, Souza IA, Chen L, Zamponi GW. 2018. BK potassium channels suppress Ca_vα2δ subunit function to reduce inflammatory and neuropathic pain. Cell Rep. 22:1956–64
    [Google Scholar]
21. 21.

    Wallner M, Meera P, Toro L. 1996. Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca²⁺-sensitive K⁺ channels: an additional transmembrane region at the N terminus. PNAS 93:14922–27
    [Google Scholar]
22. 22.

    Horrigan FT, Aldrich RW. 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]
23. 23.

    Ma Z, Lou XJ, Horrigan FT. 2006. Role of charged residues in the S1–S4 voltage sensor of BK channels. J. Gen. Physiol. 127:309–28
    [Google Scholar]
24. 24.

    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]
25. 25.

    Hite RK, Tao X, MacKinnon R. 2017. Structural basis for gating the high-conductance Ca²⁺-activated K⁺ channel. Nature 541:52–57
    [Google Scholar]
26. 26.

    Yang H, Shi J, Zhang G, Yang J, Delaloye K, Cui J. 2008. Activation of Slo1 BK channels by Mg²⁺ coordinated between the voltage sensor and RCK1 domains. Nat. Struct. Mol. Biol. 15:1152–9
    [Google Scholar]
27. 27.

    Sun L, Horrigan FT. 2022. A gating lever and molecular logic gate that couple voltage and calcium sensor activation to opening in BK potassium channels. Sci. Adv. 8:eabq5772
    [Google Scholar]
28. 28.

    Fakler B, Adelman JP. 2008. Control of K_Ca channels by calcium nano/microdomains. Neuron 59:873–81
    [Google Scholar]
29. 29.

    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]
30. 30.

    Prakriya M, Lingle CJ. 2000. Activation of BK channels in rat chromaffin cells requires summation of Ca²⁺ influx from multiple Ca²⁺ channels. J. Neurophysiol. 84:1123–35
    [Google Scholar]
31. 31.

    Irie T, Trussell LO. 2017. Double-nanodomain coupling of calcium channels, ryanodine receptors, and BK channels controls the generation of burst firing. Neuron 96:856–70
    [Google Scholar]
32. 32.

    Berkefeld H, Sailer CA, Bildl W, Rohde V, Thumfart JO et al. 2006. BK_Ca-Ca_V channel complexes mediate rapid and localized Ca²⁺-activated K⁺ signaling. Science 314:615–20
    [Google Scholar]
33. 33.

    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]
34. 34.

    Li B, Suutari BS, Sun SD, Luo Z, Wei C et al. 2020. Neuronal inactivity co-opts LTP machinery to drive potassium channel splicing and homeostatic spike widening. Cell 181:1547–65.e15
    [Google Scholar]
35. 35.

    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. 272:11710–17
    [Google Scholar]
36. 36.

    Yan J, Olsen JV, Park KS, Li W, Bildl W et al. 2008. Profiling the phospho-status of the BK_Ca channel α subunit in rat brain reveals unexpected patterns and complexity. Mol. Cell. Proteom. 7:2188–98
    [Google Scholar]
37. 37.

    Gonzalez-Perez V, Zhou Y, Ciorba MA, Lingle CJ. 2022. The LRRC family of BK channel regulatory subunits: potential roles in health and disease. J. Physiol. 600:1357–71
    [Google Scholar]
38. 38.

    Kshatri A, Cerrada A, Gimeno R, Bartolome-Martin D, Rojas P, Giraldez T. 2020. Differential regulation of BK channels by fragile X mental retardation protein. J. Gen. Physiol. 152:e201912502
    [Google Scholar]
39. 39.

    Niday Z, Bean BP. 2021. BK channel regulation of after-potentials and burst firing in cerebellar Purkinje neurons. J. Neurosci. 41:2854–69
    [Google Scholar]
40. 40.

    Whitt JP, McNally BA, Meredith AL. 2018. Differential contribution of Ca²⁺ sources to day and night BK current activation in the circadian clock. J. Gen. Physiol. 150:259–75
    [Google Scholar]
41. 41.

    Ancatén-González C, Segura I, Alvarado-Sánchez R, Chávez AE, Latorre R. 2023. Ca²⁺- and voltage-activated K⁺ (BK) channels in the nervous system: one gene, a myriad of physiological functions. Int. J. Mol. Sci. 24:3407
    [Google Scholar]
42. 42.

    Berkefeld H, Fakler B. 2013. Ligand-gating by Ca²⁺ is rate limiting for physiological operation of BK_Ca channels. J. Neurosci. 33:7358–67
    [Google Scholar]
43. 43.

    Plante AE, Whitt JP, Meredith AL. 2021. BK channel activation by L-type Ca²⁺ channels Ca_V1.2 and Ca_V1.3 during the subthreshold phase of an action potential. J. Neurophysiol. 126:427–39
    [Google Scholar]
44. 44.

    Brenner R, Perez GJ, Bonev AD, Eckman DM, Kosek JC et al. 2000. Vasoregulation by the β1 subunit of the calcium-activated potassium channel. Nature 407:870–76
    [Google Scholar]
45. 45.

    Martinez-Espinosa PL, 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]
46. 46.

    Montgomery JR, Meredith AL. 2012. Genetic activation of BK currents in vivo generates bidirectional effects on neuronal excitability. PNAS 109:18997–9002
    [Google Scholar]
47. 47.

    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]
48. 48.

    Van Goor F, Li YX, Stojilkovic SS. 2001. Paradoxical role of large-conductance calcium-activated K⁺ (BK) channels in controlling action potential-driven Ca²⁺ entry in anterior pituitary cells. J. Neurosci. 21:5902–15
    [Google Scholar]
49. 49.

    Sausbier M, Hu H, Arntz C, Feil S, Kamm S et al. 2004. Cerebellar ataxia and Purkinje cell dysfunction caused by Ca²⁺-activated K⁺ channel deficiency. PNAS 101:9474–78
    [Google Scholar]
50. 50.

    Gu N, Vervaeke K, Storm JF. 2007. BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells. J. Physiol. 580:859–82
    [Google Scholar]
51. 51.

    Jin W, Sugaya A, Tsuda T, Ohguchi H, Sugaya E. 2000. Relationship between large conductance calcium-activated potassium channel and bursting activity. Brain Res 860:21–28
    [Google Scholar]
52. 52.

    Nelson AB, Krispel CM, Sekirnjak C, du Lac S. 2003. Long-lasting increases in intrinsic excitability triggered by inhibition. Neuron 40:609–20
    [Google Scholar]
53. 53.

    Lai MH, Wu Y, Gao Z, Anderson ME, Dalziel JE, Meredith AL. 2014. BK channels regulate sinoatrial node firing rate and cardiac pacing in vivo. Am. J. Physiol. Heart Circ. Physiol. 307:H1327–38
    [Google Scholar]
54. 54.

    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]
55. 55.

    Ly C, Melman T, Barth AL, Ermentrout GB. 2011. Phase-resetting curve determines how BK currents affect neuronal firing. J. Comput. Neurosci. 30:211–23
    [Google Scholar]
56. 56.

    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]
57. 57.

    Prakriya M, Lingle CJ. 1999. BK channel activation by brief depolarizations requires Ca²⁺ influx through L- and Q-type Ca²⁺ channels in rat chromaffin cells. J. Neurophysiol. 81:2267–78
    [Google Scholar]
58. 58.

    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]
59. 59.

    Gittis AH, Moghadam SH, du Lac S. 2010. Mechanisms of sustained high firing rates in two classes of vestibular nucleus neurons: differential contributions of resurgent Na, Kv3, and BK currents. J. Neurophysiol. 104:1625–34
    [Google Scholar]
60. 60.

    Pedroarena CM. 2011. BK and Kv3.1 potassium channels control different aspects of deep cerebellar nuclear neurons action potentials and spiking activity. Cerebellum 10:647–58
    [Google Scholar]
61. 61.

    Wang B, Jaffe DB, Brenner R. 2014. Current understanding of iberiotoxin-resistant BK channels in the nervous system. Front. Physiol. 5:382
    [Google Scholar]
62. 62.

    Park SM, Roache CE, Iffland PH 2nd, Moldenhauer HJ, Matychak KK et al. 2022. BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models. eLife 11:e77953
    [Google Scholar]
63. 63.

    Dong P, Zhang Y, Hunanyan AS, Mikati MA, Cui J, Yang H. 2022. Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia. PNAS 119:e2200140119
    [Google Scholar]
64. 64.

    Du X, Carvalho-de-Souza JL, Wei C, Carrasquel-Ursulaez W, Lorenzo Y et al. 2020. Loss-of-function BK channel mutation causes impaired mitochondria and progressive cerebellar ataxia. PNAS 117:6023–34
    [Google Scholar]
65. 65.

    Whitt JP, Montgomery JR, Meredith AL. 2016. BK channel inactivation gates daytime excitability in the circadian clock. Nat. Commun. 7:10837
    [Google Scholar]
66. 66.

    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]
67. 67.

    Bellono NW, Leitch DB, Julius D. 2017. Molecular basis of ancestral vertebrate electroreception. Nature 543:391–96
    [Google Scholar]
68. 68.

    Fettiplace R. 2020. Diverse mechanisms of sound frequency discrimination in the vertebrate cochlea. Trends Neurosci. 43:88–102
    [Google Scholar]
69. 69.

    Gómez R, Maglio LE, Gonzalez-Hernandez AJ, Rivero-Pérez B, Bartolomé-Martín D, Giraldez T. 2021. NMDA receptor–BK channel coupling regulates synaptic plasticity in the barrel cortex. PNAS 118:e2107026118
    [Google Scholar]
70. 70.

    Zhang J, Guan X, Li Q, Meredith AL, Pan HL, Yan J. 2018. Glutamate-activated BK channel complexes formed with NMDA receptors. PNAS 115:E9006–14
    [Google Scholar]
71. 71.

    Griguoli M, Sgritta M, Cherubini E. 2016. Presynaptic BK channels control transmitter release: physiological relevance and potential therapeutic implications. J. Physiol. 594:3489–500
    [Google Scholar]
72. 72.

    Hu H, Shao LR, Chavoshy S, Gu N, Trieb M et al. 2001. Presynaptic Ca²⁺-activated K⁺ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release. J. Neurosci. 21:9585–97
    [Google Scholar]
73. 73.

    Marcantoni A, Vandael DH, Mahapatra S, Carabelli V, Sinnegger-Brauns MJ et al. 2010. Loss of Ca_V1.3 channels reveals the critical role of L-type and BK channel coupling in pacemaking mouse adrenal chromaffin cells. J. Neurosci. 30:491–504
    [Google Scholar]
74. 74.

    Meredith AL, Thorneloe KS, Werner ME, Nelson MT, Aldrich RW. 2004. Overactive bladder and incontinence in the absence of the BK large conductance Ca²⁺-activated K⁺ channel. J. Biol. Chem. 279:36746–52
    [Google Scholar]
75. 75.

    Benkusky NA, Korovkina VP, Brainard AM, England SK. 2002. Myometrial maxi-K channel β1 subunit modulation during pregnancy and after 17β-estradiol stimulation. FEBS Lett. 524:97–102
    [Google Scholar]
76. 76.

    Atkinson NS, Brenner R, Chang W, Wilbur J, Larimer JL, Yu J. 2000. Molecular separation of two behavioral phenotypes by a mutation affecting the promoters of a Ca-activated K channel. J. Neurosci. 20:2988–93
    [Google Scholar]
77. 77.

    Yesil G, Aralasmak A, Akyuz E, Icagasioglu D, Uygur Sahin T, Bayram Y. 2018. Expanding the phenotype of homozygous KCNMA1 mutations; dyskinesia, epilepsy, intellectual disability, cerebellar and corticospinal tract atrophy. Balkan Med. J. 35:336–39
    [Google Scholar]
78. 78.

    Tabarki B, AlMajhad N, AlHashem A, Shaheen R, Alkuraya FS. 2016. Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures. Hum. Genet. 135:1295–98
    [Google Scholar]
79. 79.

    Moldenhauer H, Tammen K, Meredith AL. 2023. Structural mapping of patient-associated KCNMA1 gene variants. Biophys. J. https://doi.org/10.1016/j.bpj.2023.11.3404
80. 80.

    Plante AE, Lai MH, Lu J, Meredith AL. 2019. Effects of single nucleotide polymorphisms in human KCNMA1 on BK current properties. Front. Mol. Neurosci. 12:285
    [Google Scholar]
81. 81.

    Laumonnier F, Roger S, Guerin P, Molinari F, M'Rad R et al. 2006. Association of a functional deficit of the BK_Ca channel, a synaptic regulator of neuronal excitability, with autism and mental retardation. Am. J. Psychiatry 163:1622–29
    [Google Scholar]
82. 82.

    Liang L, Liu H, Bartholdi D, van Haeringen A, Fernandez-Jaen A et al. 2022. Identification and functional analysis of two new de novo KCNMA1 variants associated with Liang-Wang syndrome. Acta Physiol. 235:e13800
    [Google Scholar]
83. 83.

    Yao Y, Qu D, Jing X, Jia Y, Zhong Q et al. 2021. Molecular mechanisms of epileptic encephalopathy caused by KCNMA1 loss-of-function mutations. Front. Pharmacol. 12:775328
    [Google Scholar]
84. 84.

    Yang J, Yang H, Sun X, Delaloye K, Yang X et al. 2013. Interaction between residues in the Mg²⁺-binding site regulates BK channel activation. J. Gen. Physiol. 141:217–28
    [Google Scholar]
85. 85.

    Geng Y, Li P, Butler A, Wang B, Salkoff L, Magleby KL. 2023. BK channels of five different subunit combinations underlie the de novo KCNMA1 G375R channelopathy. J. Gen. Physiol. 155:5e202213302
    [Google Scholar]
86. 86.

    Rodrigues Bento J, Feben C, Kempers M, van Rij M, Woiski M et al. 2021. Two novel presentations of KCNMA1-related pathology—expanding the clinical phenotype of a rare channelopathy. Mol. Genet. Genom. Med. 9:10e1797
    [Google Scholar]
87. 87.

    Brelidze TI, Niu X, Magleby KL. 2003. A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification. PNAS 100:9017–22
    [Google Scholar]
88. 88.

    Schreiber M, Salkoff L. 1997. A novel calcium-sensing domain in the BK channel. Biophys. J. 73:1355–63
    [Google Scholar]
89. 89.

    Xia XM, Zeng X, Lingle CJ. 2002. Multiple regulatory sites in large-conductance calcium-activated potassium channels. Nature 418:880–84
    [Google Scholar]
90. 90.

    Bao L, Kaldany C, Holmstrand EC, Cox DH. 2004. Mapping the BK_Ca channel's ‘Ca²⁺ bowl’: side-chains essential for Ca²⁺ sensing. J. Gen. Physiol. 123:475–89
    [Google Scholar]
91. 91.

    Yusifov T, Savalli N, Gandhi CS, Ottolia M, Olcese R. 2008. The RCK2 domain of the human BK_Ca channel is a calcium sensor. PNAS 105:376–81
    [Google Scholar]
92. 92.

    Wang B, Rothberg BS, Brenner R. 2009. Mechanism of increased BK channel activation from a channel mutation that causes epilepsy. J. Gen. Physiol. 133:283–94
    [Google Scholar]
93. 93.

    Yang J, Krishnamoorthy G, Saxena A, Zhang G, Shi J et al. 2010. An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca²⁺ sensing. Neuron 66:871–83
    [Google Scholar]
94. 94.

    Buckley C, Williams J, Munteanu T, King M, Park SM et al. 2020. Status dystonicus, oculogyric crisis and paroxysmal dyskinesia in a 25 year-old woman with a novel KCNMA1 variant, K457E. Tremor Other Hyperkinet. Mov. 10:49
    [Google Scholar]
95. 95.

    Yucesan E, Goncu B, Ozgul C, Kebapci A, Aslanger AD et al. 2023. Functional characterization of KCNMA1 mutation associated with dyskinesia, seizure, developmental delay, and cerebellar atrophy. Int. J. Neurosci. https://doi.org/10.1080/00207454.2023.2221814
    [Google Scholar]
96. 96.

    Liu HW, Hou PP, Guo XY, Zhao ZW, Hu B et al. 2014. Structural basis for calcium and magnesium regulation of a large conductance calcium-activated potassium channel with beta1 subunits. J. Biol. Chem. 289:16914–23
    [Google Scholar]
97. 97.

    Tang QY, Zhang Z, Meng XY, Cui M, Logothetis DE. 2014. Structural determinants of phosphatidyl-inositol 4,5-bisphosphate (PIP₂) regulation of BK channel activity through the RCK1 Ca²⁺ coordination site. J. Biol. Chem. 289:18860–72
    [Google Scholar]
98. 98.

    Zhang G, Gibson RA, McDonald M, Liang P, Kang PW et al. 2020. A gain-of-function mutation in KCNMA1 causes dystonia spells controlled with stimulant therapy. Mov. Disord. 35:1868–73
    [Google Scholar]
99. 99.

    Moldenhauer HJ, Matychak KK, Meredith AL. 2020. Comparative gain-of-function effects of the KCNMA1-N999S mutation on human BK channel properties. J. Neurophysiol. 123:560–70
    [Google Scholar]
100. 100.

     Li X, Poschmann S, Chen Q, Fazeli W, Oundjian NJ et al. 2018. De novo BK channel variant causes epilepsy by affecting voltage gating but not Ca²⁺ sensitivity. Eur. J. Hum. Genet. 26:220–29
     [Google Scholar]
101. 101.

     Zhang G, Geng Y, Jin Y, Shi J, McFarland K et al. 2017. Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels. J. Gen. Physiol. 149:373–87
     [Google Scholar]
102. 102.

     Budelli G, Geng Y, Butler A, Magleby KL, Salkoff L. 2013. Properties of Slo1 K⁺ channels with and without the gating ring. PNAS 110:16657–62
     [Google Scholar]
103. 103.

     Geng Y, Deng Z, Zhang G, Budelli G, Butler A et al. 2020. Coupling of Ca²⁺ and voltage activation in BK channels through the αB helix/voltage sensor interface. PNAS 117:2514512–21
     [Google Scholar]
104. 104.

     Keros S, Heim J, Hakami W, Zohar-Dayan E, Ben-Zeev B et al. 2022. Lisdexamfetamine therapy in paroxysmal non-kinesigenic dyskinesia associated with the KCNMA1-N999S variant. Mov. Disord. Clin. Pract. 9:229–35
     [Google Scholar]
105. 105.

     Wang J, Yu S, Zhang Q, Chen Y, Bao X, Wu X. 2017. KCNMA1 mutation in children with paroxysmal dyskinesia and epilepsy: case report and literature review. Transl. Sci. Rare Dis. 2:8
     [Google Scholar]
106. 106.

     Zhang ZB, Tian MQ, Gao K, Jiang YW, Wu Y. 2015. De novo KCNMA1 mutations in children with early-onset paroxysmal dyskinesia and developmental delay. Mov. Disord. 30:1290–92
     [Google Scholar]
107. 107.

     Heim J, Vemuri A, Lewis S, Guida B, Troester M et al. 2020. Cataplexy in patients harboring the KCNMA1 p.N999S mutation. Mov. Disord. Clin. Pract. 7:861–62
     [Google Scholar]
108. 108.

     de Gusmao CM. 2022. Teaching video neuroimage: dystonic cataplexy in KCNMA1 paroxysmal movement disorder. Neurology 99:221010–11
     [Google Scholar]
109. 109.

     Liao JY, Salles PA, Shuaib UA, Fernandez HH. 2021. Genetic updates on paroxysmal dyskinesias. J. Neural. Transm. 128:447–71
     [Google Scholar]
110. 110.

     Erro R, Bhatia KP. 2019. Unravelling of the paroxysmal dyskinesias. J. Neurol. Neurosurg. Psychiatry 90:227–34
     [Google Scholar]
111. 111.

     Mameli C, Cazzola R, Spaccini L, Calcaterra V, Macedoni M et al. 2021. Neonatal diabetes in patients affected by Liang-Wang syndrome carrying KCNMA1 variant p.(Gly375Arg) suggest a potential role of Ca²⁺ and voltage-activated K⁺ channel activity in human insulin secretion. Curr. Issues Mol. Biol. 43:1036–42
     [Google Scholar]
112. 112.

     Graber D, Imagawa E, Miyake N, Matsumoto N, Miyatake S et al. 2022. Polymicrogyria in a child with KCNMA1-related channelopathy. Brain Dev. 44:173–77
     [Google Scholar]
113. 113.

     Al-Attas AA, Aldayel AY, Eskandrani AM, Biary N. 2022. KCNMA1-related refractory status epilepticus responding to vagal nerve stimulation: case report and literature review. Neurosciences 27:275–78
     [Google Scholar]
114. 114.

     Tian WT, Huang XJ, Mao X, Liu Q, Liu XL et al. 2018. Proline-rich transmembrane protein 2-negative paroxysmal kinesigenic dyskinesia: clinical and genetic analyses of 163 patients. Mov. Disord. 33:459–67
     [Google Scholar]
115. 115.

     Reiss S, Bornstein E, Meredith AL. 2021. Prenatal diagnostic testing challenges with novel gene alterations in KCNMA1-linked channelopathy: a case report. Mol. Genet. Metab. 132:S317–18
     [Google Scholar]
116. 116.

     Ling L, Bugay V, Wang B, Chuang H, Brenner R. 2016. A novel transgenic mouse model of the human potassium channel gain-of-function epilepsy mutation D434G Presented at the American Epilepsy Society Meeting Dec., Abstract 3.026. https://aesnet.org/abstractslisting/a-novel-transgenic-mouse-model-of-the-human-bk-potassium-channel-gain-of-function-epilepsy-mutation-d434g
117. 117.

     Kratschmer P, Lowe SA, Buhl E, Chen KF, Kullmann DM et al. 2021. Impaired pre-motor circuit activity and movement in a Drosophila model of KCNMA1-linked dyskinesia. Mov. Disord. 36:1158–69
     [Google Scholar]
118. 118.

     Zemen BG, Lai MH, Whitt JP, Khan Z, Zhao G, Meredith AL. 2015. Generation of Kcnma1^fl-tdTomato, a conditional deletion of the BK channel α subunit in mouse. Physiol. Rep. 3:11e12612
     [Google Scholar]
119. 119.

     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]
120. 120.

     Imlach WL, Finch SC, Dunlop J, Meredith AL, Aldrich RW, Dalziel JE. 2008. The molecular mechanism of ‘Ryegrass Staggers,’ a neurological disorder of K⁺ channels. J. Pharmacol. Exp. Ther. 327:657–64
     [Google Scholar]
121. 121.

     Wang X, Burke SRA, Talmadge RJ, Voss AA, Rich MM. 2020. Depressed neuromuscular transmission causes weakness in mice lacking BK potassium channels. J. Gen. Physiol. 152:e201912526
     [Google Scholar]
122. 122.

     Typlt M, Mirkowski M, Azzopardi E, Ruettiger L, Ruth P, Schmid S. 2013. Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory. PLOS ONE 8:e81270
     [Google Scholar]
123. 123.

     Kuebler D, Zhang H, Ren X, Tanouye MA. 2001. Genetic suppression of seizure susceptibility in Drosophila. J. Neurophysiol. 86:1211–25
     [Google Scholar]
124. 124.

     Ghezzi A, Krishnan HR, Atkinson NS. 2014. Susceptibility to ethanol withdrawal seizures is produced by BK channel gene expression. Addict. Biol. 19:332–37
     [Google Scholar]
125. 125.

     Sheehan JJ, Benedetti BL, Barth AL. 2009. Anticonvulsant effects of the BK-channel antagonist paxilline. Epilepsia 50:711–20
     [Google Scholar]
126. 126.

     Ermolinsky BS, Skinner F, Garcia I, Arshadmansab MF, Otalora LF et al. 2011. Upregulation of STREX splice variant of the large conductance Ca²⁺-activated potassium (BK) channel in a rat model of mesial temporal lobe epilepsy. Neurosci. Res. 69:73–80
     [Google Scholar]
127. 127.

     Ermolinsky B, Arshadmansab MF, Pacheco Otalora LF, Zarei MM, Garrido-Sanabria ER. 2008. Deficit of Kcnma1 mRNA expression in the dentate gyrus of epileptic rats. Neuroreport 19:1291–94
     [Google Scholar]
128. 128.

     Pacheco Otalora LF, Hernandez EF, Arshadmansab MF, Francisco S, Willis M et al. 2008. Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy. Brain Res. 1200:116–31
     [Google Scholar]
129. 129.

     Sun AX, Yuan Q, Fukuda M, Yu W, Yan H et al. 2019. Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science 366:1486–92
     [Google Scholar]
130. 130.

     Perche O, Lesne F, Patat A, Raab S, Twyman R et al. 2022. Large-conductance calcium-activated potassium channel haploinsufficiency leads to sensory deficits in the visual system: a case report. J. Med. Case Rep. 16:180
     [Google Scholar]
131. 131.

     Deng PY, Klyachko VA. 2016. Genetic upregulation of BK channel activity normalizes multiple synaptic and circuit defects in a mouse model of fragile X syndrome. J. Physiol. 594:83–97
     [Google Scholar]
132. 132.

     Melman A, Bar-Chama N, McCullough A, Davies K, Christ G. 2007. Plasmid-based gene transfer for treatment of erectile dysfunction and overactive bladder: results of a phase I trial. Isr. Med. Assoc. J. 9:143–46
     [Google Scholar]
133. 133.

     Cuppoletti J, Malinowska DH, Tewari KP, Chakrabarti J, Ueno R. 2007. Cellular and molecular effects of unoprostone as a BK channel activator. Biochim. Biophys. Acta Biomembr. 1768:1083–92
     [Google Scholar]
134. 134.

     Al-Karagholi MA, Ghanizada H, Waldorff Nielsen CA, Skandarioon C, Snellman J et al. 2021. Opening of BK_Ca channels causes migraine attacks: a new downstream target for the treatment of migraine. Pain 162:2512–20
     [Google Scholar]
135. 135.

     Ptacek LJ. 2015. Episodic disorders: channelopathies and beyond. Annu. Rev. Physiol. 77:475–79
     [Google Scholar]
136. 136.

     Bushart DD, Huang H, Man LJ, Morrison LM, Shakkottai VG. 2020. A chlorzoxazone-baclofen combination improves cerebellar impairment in spinocerebellar ataxia type 1. Mov. Disord. 36:622–31
     [Google Scholar]
137. 137.

     Shruti S, Clem RL, Barth AL. 2008. A seizure-induced gain-of-function in BK channels is associated with elevated firing activity in neocortical pyramidal neurons. Neurobiol. Dis. 30:323–30
     [Google Scholar]
138. 138.

     Zhu Y, Zhang S, Feng Y, Xiao Q, Cheng J, Tao J. 2018. The yin and yang of BK channels in epilepsy. CNS Neurol. Disord. Drug Targets 17:272–79
     [Google Scholar]
139. 139.

     Godfraind T. 2017. Discovery and development of calcium channel blockers. Front. Pharmacol. 8:286
     [Google Scholar]
140. 140.

     Ovsiew F, Meador KJ, Sethi K. 1998. Verapamil for severe hyperkinetic movement disorders. Mov. Disord. 13:341–44
     [Google Scholar]
141. 141.

     Abad V, Ovsiew F. 1993. Treatment of persistent myoclonic tardive dystonia with verapamil. Br. J. Psychiatry 162:554–56
     [Google Scholar]
142. 142.

     Narayanan J, Frech R, Walters S, Patel V, Frigerio R, Maraganore DM. 2016. Low dose verapamil as an adjunct therapy for medically refractory epilepsy—an open label pilot study. Epilepsy Res. 126:197–200
     [Google Scholar]
143. 143.

     Lakshmikanthcharan S, Hisham M, Chaitanya Juluri SK, Nandakumar SM. 2018. Verapamil as an adjuvant treatment for drug-resistant epilepsy. Indian J. Crit. Care Med. 22:680–82
     [Google Scholar]
144. 144.

     Kulak W, Sobaniec W, Wojtal K, Czuczwar SJ. 2004. Calcium modulation in epilepsy. Pol. J. Pharmacol. 56:29–41
     [Google Scholar]
145. 145.

     Masoud M, Prange L, Wuchich J, Hunanyan A, Mikati MA. 2017. Diagnosis and treatment of alternating hemiplegia of childhood. Curr. Treat. Opt. Neurol. 19:8
     [Google Scholar]
146. 146.

     Harper AA, Catacuzzeno L, Trequattrini C, Petris A, Franciolini F. 2001. Verapamil block of large-conductance Ca²⁺-activated K⁺ channels in rat aortic myocytes. J. Membr. Biol. 179:103–11
     [Google Scholar]
147. 147.

     Wang ZW, Saifee O, Nonet ML, Salkoff L. 2001. SLO-1 potassium channels control quantal content of neurotransmitter release at the C. elegans neuromuscular junction. Neuron 32:867–81
     [Google Scholar]
148. 148.

     Scott LL, Brecht EJ, Philpo A, Iyer S, Wu NS et al. 2017. A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus. Sci. Rep. 7:42433
     [Google Scholar]
149. 149.

     Ghezzi A, Al-Hasan YM, Larios LE, Bohm RA, Atkinson NS. 2004. slo K⁺ channel gene regulation mediates rapid drug tolerance. PNAS 101:17276–81
     [Google Scholar]