large conductance calcium activated potassium channels


Summary: A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.

Top Publications

  1. Benkusky N, Fergus D, Zucchero T, England S. Regulation of the Ca2+-sensitive domains of the maxi-K channel in the mouse myometrium during gestation. J Biol Chem. 2000;275:27712-9 pubmed
  2. Liu G, Niu X, Wu R, Chudasama N, Yao Y, Jin X, et al. Location of modulatory beta subunits in BK potassium channels. J Gen Physiol. 2010;135:449-59 pubmed publisher
    ..Thus, each beta lies between and can interact with the voltage-sensing domains of two adjacent alpha subunits. ..
  3. Martin G, O Connell R, Pietrzykowski A, Treistman S, Ethier M, Madison J. Interleukin-4 activates large-conductance, calcium-activated potassium (BKCa) channels in human airway smooth muscle cells. Exp Physiol. 2008;93:908-18 pubmed publisher
    ..These findings are consistent with a model in which IL-4 rapidly increases near-membrane calcium concentrations to regulate BK(Ca) activity. ..
  4. Wu R, Chudasama N, Zakharov S, Doshi D, Motoike H, Liu G, et al. Location of the beta 4 transmembrane helices in the BK potassium channel. J Neurosci. 2009;29:8321-8 pubmed publisher
    ..That disulfide crosslinking caused only small functional perturbations is consistent with the proximity of the extracellular ends of TM2 to S0 and of TM1 to S1 and to S2, in both the open and closed states. ..
  5. Cui J, Yang H, Lee U. Molecular mechanisms of BK channel activation. Cell Mol Life Sci. 2009;66:852-75 pubmed publisher
    ..This review summarizes the current understanding of these structural domains and their mutual interactions in voltage-, Ca(2+)- and Mg(2+)-dependent activation of the channel. ..
  6. Wu Y, Xiong Y, Wang S, Yi H, Li H, Pan N, et al. Intersubunit coupling in the pore of BK channels. J Biol Chem. 2009;284:23353-63 pubmed publisher
    ..These findings provide a basis for understanding the structure and gating of the BK channel pore. ..
  7. Tang Q, Zhang Z, Xia X, Lingle C. Block of mouse Slo1 and Slo3 K+ channels by CTX, IbTX, TEA, 4-AP and quinidine. Channels (Austin). 2010;4:22-41 pubmed
    ..The quinidine concentrations effective in blocking Slo3 suggest, that in experiments that have examined quinidine effects on sperm, any Slo3 currents would be almost completely inhibited. ..
  8. Yuill K, McNeish A, Kansui Y, Garland C, Dora K. Nitric oxide suppresses cerebral vasomotion by sGC-independent effects on ryanodine receptors and voltage-gated calcium channels. J Vasc Res. 2010;47:93-107 pubmed publisher
    ..NO exerts sGC-independent actions at RYRs and at VGCC, both of which normally suppress cerebral artery myogenic tone. ..
  9. Matthews E, Disterhoft J. Blocking the BK channel impedes acquisition of trace eyeblink conditioning. Learn Mem. 2009;16:106-9 pubmed publisher
    ..This suggests that nonspecific increases in excitability and baseline neuronal firing rates caused by in vivo blockade of the BK channel may disrupt correct processing of inputs, thereby impairing hippocampus-dependent learning. ..

More Information


  1. Kathiresan T, Harvey M, Orchard S, Sakai Y, Sokolowski B. A protein interaction network for the large conductance Ca(2+)-activated K(+) channel in the mouse cochlea. Mol Cell Proteomics. 2009;8:1972-87 pubmed publisher
    ..The studies described herein provide insights into BK-related functions that include not only cell excitation, but also cell signaling and apoptosis, and involve proteins concerned with Ca(2+) regulation, structure, and hearing loss. ..
  2. Kaufmann W, Ferraguti F, Fukazawa Y, Kasugai Y, Shigemoto R, Laake P, et al. Large-conductance calcium-activated potassium channels in purkinje cell plasma membranes are clustered at sites of hypolemmal microdomains. J Comp Neurol. 2009;515:215-30 pubmed publisher
    ..Clustered BK channels in the plasma membrane may thus participate in building a functional unit (plasmerosome) with the underlying calciosome that contributes significantly to local signaling in Purkinje cells. ..
  3. Zhou Y, Tang Q, Xia X, Lingle C. Glycine311, a determinant of paxilline block in BK channels: a novel bend in the BK S6 helix. J Gen Physiol. 2010;135:481-94 pubmed publisher
  4. Edelstein S, Changeux J. Relationships between structural dynamics and functional kinetics in oligomeric membrane receptors. Biophys J. 2010;98:2045-52 pubmed publisher
    ..Concerning published varphi(F) values underlying the conformational wave hypothesis for nicotinic receptors, we note that interpretations may be complicated by variations in the width of harmonic energy profiles. ..
  5. Fodor A, Aldrich R. Convergent evolution of alternative splices at domain boundaries of the BK channel. Annu Rev Physiol. 2009;71:19-36 pubmed publisher
  6. Smeda J, McGuire J, Daneshtalab N. Protease-activated receptor 2 and bradykinin-mediated vasodilation in the cerebral arteries of stroke-prone rats. Peptides. 2010;31:227-37 pubmed publisher
    ..Despite the presence of vascular injury, edema, inflammation and the loss of endothelium-dependent bradykinin vasodilation we found no evidence that PAR(2) expression or vascular function was altered in MCA after stroke. ..
  7. Imig J, Dimitropoulou C, Reddy D, White R, Falck J. Afferent arteriolar dilation to 11, 12-EET analogs involves PP2A activity and Ca2+-activated K+ Channels. Microcirculation. 2008;15:137-50 pubmed publisher
    ..These data support the concept that 11, 12-EET utilizes PP2A dependent pathways to activate large-conductance KCa channels and dilate the afferent arteriole. ..
  8. Yang J, Krishnamoorthy G, Saxena A, Zhang G, Shi J, Yang H, et al. An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing. Neuron. 2010;66:871-83 pubmed publisher
    ..The GEPD mutation alters such a response, suggesting that a less flexible AC region may be more effective in coupling Ca(2+) binding to channel opening. ..
  9. Namiranian K, Lloyd E, Crossland R, Marrelli S, Taffet G, Reddy A, et al. Cerebrovascular responses in mice deficient in the potassium channel, TREK-1. Am J Physiol Regul Integr Comp Physiol. 2010;299:R461-9 pubmed publisher
    ..There was no sign of TREK-1-like currents in CVSMCs from WT mice, and there were no major differences in currents between the genotypes. We conclude that regulation of arterial diameter is not altered in mice lacking TREK-1. ..
  10. Yeung C, Law J, Sam S, Ingebrandt S, Lau H, Rudd J, et al. Modulatory action of potassium channel openers on field potential and histamine release from rat peritoneal mast cells. Can J Physiol Pharmacol. 2009;87:624-32 pubmed publisher
    ..It is possible that KCO hyperpolarizes the cell membrane, enhances Ca2+ influx, and thus increases histamine release. As such, selective blockers of K+ channels may be useful for the treatment of immunological disorders...
  11. Feher A, Rutkai I, Beleznai T, Ungvari Z, Csiszar A, Edes I, et al. Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: implications in diet-induced obesity. Cardiovasc Res. 2010;87:732-9 pubmed publisher
    ..In obesity, a reduced expression of Cav-1 leads to greater contribution of the BK(Ca) channel to EDHF-mediated response, which seems essential for maintained coronary dilation. ..
  12. Liu W, Wei Y, Sun P, Wang W, Kleyman T, Satlin L. Mechanoregulation of BK channel activity in the mammalian cortical collecting duct: role of protein kinases A and C. Am J Physiol Renal Physiol. 2009;297:F904-15 pubmed publisher
    ..The specific targets of the kinases remain to be identified. ..
  13. Ye H, Jalini S, Mylvaganam S, Carlen P. Activation of large-conductance Ca(2+)-activated K(+) channels depresses basal synaptic transmission in the hippocampal CA1 area in APP (swe/ind) TgCRND8 mice. Neurobiol Aging. 2010;31:591-604 pubmed publisher
    ..The potential candidates that mediate the activation of BK channels in these pre-plaque Alzheimer's disease model mice might involve impaired calcium homeostasis and AD related over-generation of reactive oxygen species. ..
  14. Aldakkak M, Stowe D, Cheng Q, Kwok W, Camara A. Mitochondrial matrix K+ flux independent of large-conductance Ca2+-activated K+ channel opening. Am J Physiol Cell Physiol. 2010;298:C530-41 pubmed publisher
  15. Noble K, Floyd R, Shmygol A, Shmygol A, Mobasheri A, Wray S. Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium. Cell Calcium. 2010;47:47-54 pubmed publisher
    ..They contribute more to quiescence that BK channels...
  16. Cheron G, Sausbier M, Sausbier U, Neuhuber W, Ruth P, Dan B, et al. BK channels control cerebellar Purkinje and Golgi cell rhythmicity in vivo. PLoS ONE. 2009;4:e7991 pubmed publisher
    ..We hypothesize that the temporal coding modification of the spike firing of both Purkinje and Golgi cells leads to the pharmacologically or genetically induced ataxia. ..
  17. Sitdikova G, Weiger T, Hermann A. Hydrogen sulfide increases calcium-activated potassium (BK) channel activity of rat pituitary tumor cells. Pflugers Arch. 2010;459:389-97 pubmed publisher
    ..Our data show that H(2)S augments BK channel activity, and this effect can be linked to its reducing action on sulfhydryl groups of the channel protein. ..
  18. Treistman S, Martin G. BK Channels: mediators and models for alcohol tolerance. Trends Neurosci. 2009;32:629-37 pubmed publisher
    ..Although alcohol is the focus of this review, it is highly probable, given the common neural and biochemical pathways used by drugs of abuse, that the findings described here will also apply to other drugs. ..
  19. Wulf Johansson H, Hay Schmidt A, Poulsen A, Klaerke D, Olesen J, Jansen Olesen I. Expression of BK Ca channels and the modulatory beta-subunits in the rat and porcine trigeminal ganglion. Brain Res. 2009;1292:1-13 pubmed publisher
    ..The present study showed BK(Ca) channel expression in rat and porcine TG. The main modulatory beta-subunits detected in TG of both species were beta2- and beta 4-subunits. ..
  20. Chatterjee O, Taylor L, Ahmed S, Nagaraj S, Hall J, Finckbeiner S, et al. Social stress alters expression of large conductance calcium-activated potassium channel subunits in mouse adrenal medulla and pituitary glands. J Neuroendocrinol. 2009;21:167-76 pubmed publisher
    ..These data suggest that early stress will differentially affect neuroendocrine cell excitability, and call for detailed analysis of functional consequences...
  21. Gui P, Chao J, Wu X, Yang Y, Davis G, Davis M. Coordinated regulation of vascular Ca2+ and K+ channels by integrin signaling. Adv Exp Med Biol. 2010;674:69-79 pubmed
  22. Martínez López P, Santi C, Trevino C, Ocampo Gutiérrez A, Acevedo J, Alisio A, et al. Mouse sperm K+ currents stimulated by pH and cAMP possibly coded by Slo3 channels. Biochem Biophys Res Commun. 2009;381:204-9 pubmed publisher
    ..This current is also stimulated by cAMP. All of these properties match those displayed by heterologously expressed Slo3 channels, suggesting that the native current we observe in sperm is indeed carried by Slo3 channels. ..
  23. Hammami S, Willumsen N, Olsen H, Morera F, Latorre R, Klaerke D. Cell volume and membrane stretch independently control K+ channel activity. J Physiol. 2009;587:2225-31 pubmed publisher
    ..We conclude that stretch and volume sensitivity can be considered two independent regulatory mechanisms. ..
  24. Hill M, Yang Y, Ella S, Davis M, Braun A. Large conductance, Ca2+-activated K+ channels (BKCa) and arteriolar myogenic signaling. FEBS Lett. 2010;584:2033-42 pubmed publisher
    ..Knowledge of such variability will be important to exploiting the BK(Ca) channel as a therapeutic target and understanding systemic effects of its pharmacological manipulation. ..
  25. Wang Y, Zhang H, Su X, Deng X, Yuan B, Zhang W, et al. Experimental diabetes mellitus down-regulates large-conductance Ca2+-activated K+ channels in cerebral artery smooth muscle and alters functional conductance. Curr Neurovasc Res. 2010;7:75-84 pubmed
  26. Zhang H, Chen X, Hu G, Wang Y. Magnesium lithospermate B dilates mesenteric arteries by activating BKCa currents and contracts arteries by inhibiting K(V) currents. Acta Pharmacol Sin. 2010;31:665-70 pubmed publisher
    ..To examine the involvement of K(+) channels and endothelium in the vascular effects of magnesium lithospermate B (MLB), a hydrophilic active component of Salviae miltiorrhiza Radix...
  27. Lu T, Zhang D, Wang X, He T, Wang R, Chai Q, et al. Regulation of coronary arterial BK channels by caveolae-mediated angiotensin II signaling in diabetes mellitus. Circ Res. 2010;106:1164-73 pubmed publisher
    ..These results identified a molecular scheme of receptor/enzyme/channel/caveolae microdomain complex that facilitates the development of vascular BK channel dysfunction in diabetes. ..
  28. Girouard H, Bonev A, Hannah R, Meredith A, Aldrich R, Nelson M. Astrocytic endfoot Ca2+ and BK channels determine both arteriolar dilation and constriction. Proc Natl Acad Sci U S A. 2010;107:3811-6 pubmed publisher
  29. Wynne P, Puig S, Martin G, Treistman S. Compartmentalized beta subunit distribution determines characteristics and ethanol sensitivity of somatic, dendritic, and terminal large-conductance calcium-activated potassium channels in the rat central nervous system. J Pharmacol Exp Ther. 2009;329:978-86 pubmed publisher
    ..This hypothesis is supported immunohistochemically by the appearance of distinct punctate beta1 or beta4 channel clusters in the membrane of somatic and dendritic or nerve terminal compartments, respectively. ..
  30. PIETRZYKOWSKI A. The role of microRNAs in drug addiction: a big lesson from tiny molecules. Int Rev Neurobiol. 2010;91:1-24 pubmed publisher
    ..Emphasis is put on the potential of microRNAs in explaining the polygenic nature of alcoholism and prospects of microRNA research and future directions of this burgeoning field. ..
  31. Koszela Piotrowska I, Matkovic K, Szewczyk A, Jarmuszkiewicz W. A large-conductance calcium-activated potassium channel in potato (Solanum tuberosum) tuber mitochondria. Biochem J. 2009;424:307-16 pubmed publisher
    ..These results suggest that a large-conductance calcium-activated potassium channel similar to that of mammalian mitochondria is present in potato tuber mitochondria. ..
  32. Schweizer F, Savin D, Luu C, Sultemeier D, Hoffman L. Distribution of high-conductance calcium-activated potassium channels in rat vestibular epithelia. J Comp Neurol. 2009;517:134-45 pubmed publisher
    ..The predominance of BK-positive hair cells within the medial striola of juvenile animals suggests that they contribute to a scheme of highly lateralized coding of linear head movements during late development. ..
  33. Kim J, Beyer R, Morales M, Chen S, Liu L, Duncan R. Expression of BK-type calcium-activated potassium channel splice variants during chick cochlear development. J Comp Neurol. 2010;518:2554-69 pubmed publisher
    ..These results indicate that delays in protein synthesis and trafficking/scaffolding of channel subunits underlie the late acquisition of BK currents in cochlear hair cells. ..
  34. Kaufmann W, Kasugai Y, Ferraguti F, Storm J. Two distinct pools of large-conductance calcium-activated potassium channels in the somatic plasma membrane of central principal neurons. Neuroscience. 2010;169:974-86 pubmed publisher
    ..This study indicates a common organizational principle for somatic BK(Ca) channels in central principal neurons with the formation of a clustered and a scattered pool of channels, and a cell-type specific density of this channel type. ..
  35. Vang A, Mazer J, Casserly B, Choudhary G. Activation of endothelial BKCa channels causes pulmonary vasodilation. Vascul Pharmacol. 2010;53:122-9 pubmed publisher
    ..Pulmonary endothelium expresses BK(Ca) channels. Activation of endothelial BK(Ca) channels causes hyperpolarization and NO mediated endothelium-dependent vasodilation in micro- and macrovasculature in the lung. ..
  36. Xie M, Ma Y, Gao F, Bai Y, Cheng J, Chang Y, et al. Activation of BKCa channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats. Am J Physiol Cell Physiol. 2010;298:C1489-500 pubmed publisher
    ..In conclusion, activation of BK(Ca) channels is associated with increased apoptosis in cerebral VSMCs of simulated microgravity rats. ..
  37. Chen L, Jeffries O, Rowe I, Liang Z, Knaus H, Ruth P, et al. Membrane trafficking of large conductance calcium-activated potassium channels is regulated by alternative splicing of a transplantable, acidic trafficking motif in the RCK1-RCK2 linker. J Biol Chem. 2010;285:23265-75 pubmed publisher
    ..Thus alternative splicing of the intracellular RCK1-RCK2 linker plays a critical role in determining cell surface expression of BK channels by controlling the inclusion/exclusion of multiple trafficking motifs. ..
  38. Jeffries O, Geiger N, Rowe I, Tian L, McClafferty H, Chen L, et al. Palmitoylation of the S0-S1 linker regulates cell surface expression of voltage- and calcium-activated potassium (BK) channels. J Biol Chem. 2010;285:33307-14 pubmed publisher
  39. Zhang G, Huang S, Yang J, Shi J, Yang X, Moller A, et al. Ion sensing in the RCK1 domain of BK channels. Proc Natl Acad Sci U S A. 2010;107:18700-5 pubmed publisher
  40. Tang Q, Zhang Z, Xia J, Ren D, Logothetis D. Phosphatidylinositol 4,5-bisphosphate activates Slo3 currents and its hydrolysis underlies the epidermal growth factor-induced current inhibition. J Biol Chem. 2010;285:19259-66 pubmed publisher
    ..Overall, our results suggest that PIP(2) is an important regulator for Slo3 activation and that receptor-mediated hydrolysis of PIP(2) leads to inhibition of Slo3 currents both in native and heterologous expression systems. ..
  41. Eichhorn B, Muller G, Leuner A, Sawamura T, Ravens U, Morawietz H. Impaired vascular function in small resistance arteries of LOX-1 overexpressing mice on high-fat diet. Cardiovasc Res. 2009;82:493-502 pubmed publisher
    ..LOX-1 overexpression and FD caused functional changes in endothelial and vascular smooth muscle cells of small resistance arteries. ..
  42. Dismuke W, Sharif N, Ellis D. Human trabecular meshwork cell volume decrease by NO-independent soluble guanylate cyclase activators YC-1 and BAY-58-2667 involves the BKCa ion channel. Invest Ophthalmol Vis Sci. 2009;50:3353-9 pubmed publisher
    ..Unlike the YC-1 response, ODQ potentiated the BAY-58-2667-induced decreases in cell volume. These data suggest that the NO-independent decrease in TM cell volume is mediated by the sGC/cGMP/PKG pathway and involves K(+) efflux. ..
  43. Park J, Park S, Chung M, Jung K, Choi M, Kim Y, et al. High expression of large-conductance Ca2+-activated K+ channel in the CD133+ subpopulation of SH-SY5Y neuroblastoma cells. Biochem Biophys Res Commun. 2010;396:637-42 pubmed publisher
    ..The physiological implications of the differential expression of BK(Ca) and Nav1.7 in CSCs require further investigation. ..
  44. Biverståhl H, Lind J, Bodor A, Mäler L. Biophysical studies of the membrane location of the voltage-gated sensors in the HsapBK and KvAP K(+) channels. Biochim Biophys Acta. 2009;1788:1976-86 pubmed publisher
    ..The present study demonstrates that the fragments derived from the full-length proteins interact with the bilayered interior of model membranes, and that they affect both the local mobility and lipid order of model membrane systems...
  45. Santi C, Butler A, Kuhn J, Wei A, Salkoff L. Bovine and mouse SLO3 K+ channels: evolutionary divergence points to an RCK1 region of critical function. J Biol Chem. 2009;284:21589-98 pubmed publisher
    ..In SLO3 channels this region may permit evolutionary changes that tune the gating properties in different species. ..
  46. Liang G, Park S, Kim J, Choi S, Suh S. Stimulation of large-conductance Ca2+-activated K+ channels by the Na+/Ca2+ exchanger inhibitor dichlorobenzamil in cultured human umbilical vein endothelial cells and mouse aortic smooth muscle cells. J Physiol Pharmacol. 2009;60:43-50 pubmed
    ..Our report would provide a consideration if they are used as NCX blocker in vascular endothelial cells or smooth muscle cells. ..
  47. Waring D, Turgeon J. Ca2+-activated K+ channels in gonadotropin-releasing hormone-stimulated mouse gonadotrophs. Endocrinology. 2009;150:2264-72 pubmed publisher
    ..In summary, in mouse gonadotrophs the GnRH-stimulated increase in [Ca(2+)](i) activates I(SK) and I(BK), which are differentially regulated by E(2) and which may be targets for E(2) positive feedback in LH secretion. ..
  48. Lee J, Ueda A, Wu C. Pre- and post-synaptic mechanisms of synaptic strength homeostasis revealed by slowpoke and shaker K+ channel mutations in Drosophila. Neuroscience. 2008;154:1283-96 pubmed publisher
  49. Walters F, Covarrubias M, Ellingson J. Potent inhibition of the aortic smooth muscle maxi-K channel by clinical doses of ethanol. Am J Physiol Cell Physiol. 2000;279:C1107-15 pubmed
    ..5 microM) were very resistant to ethanol in the presence of increased Ca(2+) (>/= 20 microM). Alcohol consumption in clinically relevant amounts may alter the contribution of maxi-K channels to the regulation of arterial tone. ..
  50. de Wit C, Griffith T. Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses. Pflugers Arch. 2010;459:897-914 pubmed publisher
    ..The present review will focus on the complex interactions between the diverse cellular signaling mechanisms that contribute to these phenomena. ..
  51. Wulf Johansson H, Amrutkar D, Hay Schmidt A, Poulsen A, Klaerke D, Olesen J, et al. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway. Neuroscience. 2010;167:1091-102 pubmed publisher
    ..Iberiotoxin induced an increase in CGRP release from the TNC that was attenuated by NS11021. Thus, BK(Ca) channels might have a role in trigeminovascular pain transmission. ..
  52. Li Q, Sun B, Wang X, Jin Z, Zhou Y, Dong L, et al. A crucial role for hydrogen sulfide in oxygen sensing via modulating large conductance calcium-activated potassium channels. Antioxid Redox Signal. 2010;12:1179-89 pubmed publisher
    ..These data suggest that H(2)S plays a crucial role in mediating the response of carotid body chemoreceptors to hypoxia via modulating the BK(Ca) channels. ..
  53. Mulholland P, Hopf F, Bukiya A, Martin G, Liu J, Dopico A, et al. Sizing up ethanol-induced plasticity: the role of small and large conductance calcium-activated potassium channels. Alcohol Clin Exp Res. 2009;33:1125-35 pubmed publisher
    ..Taken together, these studies suggest that SK and BK channels contribute to ethanol tolerance and adaptive plasticity. ..