large conductance calcium activated potassium channel alpha subunits


Summary: The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.

Top Publications

  1. Yang H, Shi J, Zhang G, Yang J, Delaloye K, Cui J. Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains. Nat Struct Mol Biol. 2008;15:1152-9 pubmed publisher
    ..These results suggest that the VSD and the cytoplasmic domains from different subunits may interact during channel gating, and the packing of VSD or the RCK1 domain to the pore in BK channels differ from that in Kv1.2 or MthK channels. ..
  2. Hou S, Vigeland L, Zhang G, Xu R, Li M, Heinemann S, et al. Zn2+ activates large conductance Ca2+-activated K+ channel via an intracellular domain. J Biol Chem. 2010;285:6434-42 pubmed publisher
    ..The results thus demonstrate that Slo1 BK channels represent a positive and direct effector of Zn(2+) signaling and may participate in sculpting cellular response to an increase in intracellular Zn(2+) concentration. ..
  3. 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. ..
  4. Wang L, Sigworth F. Structure of the BK potassium channel in a lipid membrane from electron cryomicroscopy. Nature. 2009;461:292-5 pubmed publisher
    ..7-2.0 nm. Not requiring the formation of crystals, the RSC approach promises to be useful in the structural study of many other membrane proteins as well. ..
  5. Dismuke W, Ellis D. Activation of the BK(Ca) channel increases outflow facility and decreases trabecular meshwork cell volume. J Ocul Pharmacol Ther. 2009;25:309-14 pubmed publisher
    ..BK(Ca) channel activation increases outflow facility and decreases cell volume suggesting that K(+) efflux regulates TM cell function. ..
  6. Flores C, Cid L, Sepúlveda F. Strain-dependent differences in electrogenic secretion of electrolytes across mouse colon epithelium. Exp Physiol. 2010;95:686-98 pubmed publisher
    ..The reported differences should be taken into account when choosing the genetic background of animals to be used for genetic modification. ..
  7. Yuan P, Leonetti M, Pico A, Hsiung Y, MacKinnon R. Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution. Science. 2010;329:182-6 pubmed publisher
    ..The structure suggests that the Ca2+ gating ring, in addition to regulating the pore directly, may also modulate the voltage sensor. ..
  8. Holtzclaw J, Liu L, Grimm P, Sansom S. Shear stress-induced volume decrease in C11-MDCK cells by BK-alpha/beta4. Am J Physiol Renal Physiol. 2010;299:F507-16 pubmed publisher
    ..Furthermore, these results support the use of C11 cells as in vitro models for studying BK-related functions in IC of the kidney. ..
  9. Klukovits A, Tekes K, Gunduz Cinar O, Benyhe S, Borsodi A, Deák B, et al. Nociceptin inhibits uterine contractions in term-pregnant rats by signaling through multiple pathways. Biol Reprod. 2010;83:36-41 pubmed publisher
    ..Our results demonstrate a novel action and signaling pathway for PNOC that might be a potential drug target. ..

More Information


  1. Ou J, Kumar Y, Alioua A, Sailer C, Stefani E, Toro L. Ca2+- and thromboxane-dependent distribution of MaxiK channels in cultured astrocytes: from microtubules to the plasma membrane. Glia. 2009;57:1280-95 pubmed publisher
  2. Brazier S, Telezhkin V, Mears R, Muller C, Riccardi D, Kemp P. Cysteine residues in the C-terminal tail of the human BK(Ca)alpha subunit are important for channel sensitivity to carbon monoxide. Adv Exp Med Biol. 2009;648:49-56 pubmed publisher
    ..We suggest that CO may bind to this channel subunit in a manner similar to the transition metal-dependent co-ordination which is characteristic of several enzymes, such as CO dehydrogenase. ..
  3. Miranda Rottmann S, Kozlov A, Hudspeth A. Highly specific alternative splicing of transcripts encoding BK channels in the chicken's cochlea is a minor determinant of the tonotopic gradient. Mol Cell Biol. 2010;30:3646-60 pubmed publisher
    ..Instead, a gradient in the expression of beta subunits slows BK channels toward the low-frequency apex of the cochlea. ..
  4. Wu Y, Yang Y, Ye S, Jiang Y. Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel. Nature. 2010;466:393-7 pubmed publisher
  5. Tong M, Duncan R. Tamoxifen inhibits BK channels in chick cochlea without alterations in voltage-dependent activation. Am J Physiol Cell Physiol. 2009;297:C75-85 pubmed publisher
  6. Higgins J, Tal A, Sun X, Hauck S, Hao J, Kosofosky B, et al. Temporal and spatial mouse brain expression of cereblon, an ionic channel regulator involved in human intelligence. J Neurogenet. 2010;24:18-26 pubmed publisher
    ..The results suggest that mutCRBN may cause ARNSID by disrupting the developmental regulation of BK(Ca) in brain regions that are critical for memory and learning. ..
  7. Chiu Y, Alvarez Baron C, Kim E, Dryer S. Dominant-negative regulation of cell surface expression by a pentapeptide motif at the extreme COOH terminus of an Slo1 calcium-activated potassium channel splice variant. Mol Pharmacol. 2010;77:497-507 pubmed publisher
  8. Zhou Y, XIA X, Lingle C. Inhibition of large-conductance Ca2+-activated K+ channels by nanomolar concentrations of Ag+. Mol Pharmacol. 2010;78:952-60 pubmed publisher
    ..The results from the present study suggest a possible contribution of BK channel inhibition to the cytotoxicity of Ag(+) in humans and other species. ..
  9. 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
  10. Romanenko V, Roser K, Melvin J, Begenisich T. The role of cell cholesterol and the cytoskeleton in the interaction between IK1 and maxi-K channels. Am J Physiol Cell Physiol. 2009;296:C878-88 pubmed publisher
  11. Jha S, Dryer S. The beta1 subunit of Na+/K+-ATPase interacts with BKCa channels and affects their steady-state expression on the cell surface. FEBS Lett. 2009;583:3109-14 pubmed publisher
    ..Reduced expression of endogenous NKbeta1 markedly inhibits evoked BKCa currents with no apparent effect on their gating. In addition, NKbeta1 down-regulated cells show decreased density of Slo1 subunits on the cell surface. ..
  12. Sorensen M, Leipziger J. The essential role of luminal BK channels in distal colonic K+ secretion. J Med Invest. 2009;56 Suppl:301 pubmed
  13. Foutz R, Grimm P, Sansom S. Insulin increases the activity of mesangial BK channels through MAPK signaling. Am J Physiol Renal Physiol. 2008;294:F1465-72 pubmed publisher
    ..These results indicate that insulin activates BK in the plasma membrane of MC and stimulates, via MAPK, an increase in cellular and plasma membrane BK-alpha. ..
  14. 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. ..
  15. 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. ..
  16. Rosales R, Varanda W. Allosteric control of gating mechanisms revisited: the large conductance Ca2+-activated K+ channel. Biophys J. 2009;96:3987-96 pubmed publisher
    ..This model differs from the standard Monod-Wyman-Changeux scheme in that one distinguishes when two Ca(2+) ions are bound to adjacent or diagonal subunits of the tetramer. ..
  17. Kim E, Suh J, Chiu Y, Dryer S. Regulation of podocyte BK(Ca) channels by synaptopodin, Rho, and actin microfilaments. Am J Physiol Renal Physiol. 2010;299:F594-604 pubmed publisher
    ..Synpo may regulate BK(Ca) channels through its effects on actin dynamics and by modulating interactions between BK(Ca) channels and regulatory proteins of the podocyte slit diaphragm. ..
  18. 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. ..
  19. Ridgway L, Kim E, Dryer S. MAGI-1 interacts with Slo1 channel proteins and suppresses Slo1 expression on the cell surface. Am J Physiol Cell Physiol. 2009;297:C55-65 pubmed publisher
    ..These data suggest that MAGI-1 plays a role in regulation of surface expression of BK(Ca) channels in the kidney and possibly in other tissues. ..
  20. Rohmann K, Deitcher D, Bass A. Calcium-activated potassium (BK) channels are encoded by duplicate slo1 genes in teleost fishes. Mol Biol Evol. 2009;26:1509-21 pubmed publisher
    ..Together, the results predict that teleost fish achieve a diversity of BK channel subfunction via gene duplication, rather than increased alternative splicing as witnessed for the tetrapod and invertebrate orthologue...
  21. Kizub I, Pavlova O, Ivanova I, Soloviev A. Protein kinase C-dependent inhibition of BK(Ca) current in rat aorta smooth muscle cells following gamma-irradiation. Int J Radiat Biol. 2010;86:291-9 pubmed publisher
    ..Taken together, our data indicate that one of the mechanisms leading to elevation of vascular tone and related arterial hypertension development under ionising irradiation impact is a PKC-mediated inhibition of BK(Ca) channels in VSMC. ..
  22. Ma Y, Dong L, Ye X, Deng C, Cheng J, Liu W, et al. Activation of cloned BK(Ca) channels in nitric oxide-induced apoptosis of HEK293 cells. Apoptosis. 2010;15:426-38 pubmed publisher
    ..These results indicated that activation of cloned BK(Ca) channel was involved in NO-induced apoptosis of HEK293 cells. ..
  23. Fusi F, Cavalli M, Mulholland D, Crouch N, Coombes P, Dawson G, et al. Cardamonin is a bifunctional vasodilator that inhibits Ca(v)1.2 current and stimulates K(Ca)1.1 current in rat tail artery myocytes. J Pharmacol Exp Ther. 2010;332:531-40 pubmed publisher
    ..1 current, may represent a scaffold for the design of novel drugs of potential interest for treatment of systemic hypertension. ..
  24. Naruse K, Tang Q, Sokabe M. Stress-Axis Regulated Exon (STREX) in the C terminus of BK(Ca) channels is responsible for the stretch sensitivity. Biochem Biophys Res Commun. 2009;385:634-9 pubmed publisher
    ..These results suggest that SAK(CA) senses membrane tension through an interaction between STREX and submembranous components. ..
  25. Sokolowski B, Duncan R, Chen S, Karolat J, Kathiresan T, Harvey M. The large-conductance Ca(2+)-activated K(+) channel interacts with the apolipoprotein ApoA1. Biochem Biophys Res Commun. 2009;387:671-5 pubmed publisher
    ..Additionally, immunocolocalization studies revealed BK and ApoA1 expression in both receptor cells and auditory neurons. These data suggest new avenues of investigation, given the importance of apolipoproteins in neurological diseases. ..
  26. Ko J, Ibrahim M, Park W, Ko E, Kim N, Warda M, et al. Cloning of large-conductance Ca(2+)-activated K(+) channel alpha-subunits in mouse cardiomyocytes. Biochem Biophys Res Commun. 2009;389:74-9 pubmed publisher
    ..These findings suggest that a unique BK(Ca) channel alpha-subunit is expressed in mouse cardiomyocytes. ..
  27. Li M, Tanaka Y, Alioua A, Wu Y, Lu R, Kundu P, et al. Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel trans-inhibition independent of G-protein activation. Proc Natl Acad Sci U S A. 2010;107:19096-101 pubmed publisher
    ..We propose that vasoconstrictor TP receptor and MaxiK-channel direct interaction facilitates G-protein-independent TP to MaxiK trans-inhibition, which would promote vasoconstriction. ..
  28. Yun J, Park H, Ko J, Lee W, Kim T, Shin J, et al. Expression of Ca2+ -activated K+ channels in human dermal fibroblasts and their roles in apoptosis. Skin Pharmacol Physiol. 2010;23:91-104 pubmed publisher
  29. Yang Y, Wu X, Gui P, Wu J, Sheng J, Ling S, et al. Alpha5beta1 integrin engagement increases large conductance, Ca2+-activated K+ channel current and Ca2+ sensitivity through c-src-mediated channel phosphorylation. J Biol Chem. 2010;285:131-41 pubmed publisher
  30. Kim E, Chiu Y, Dryer S. Neph1 regulates steady-state surface expression of Slo1 Ca(2+)-activated K(+) channels: different effects in embryonic neurons and podocytes. Am J Physiol Cell Physiol. 2009;297:C1379-88 pubmed publisher
    ..In podocytes, Neph1 siRNA also caused a decrease in nephrin, even though the Neph1 siRNA had no sequence homology with nephrin. However, we could not detect nephrin in ciliary ganglion neurons. ..
  31. Roth M, Rupp M, Hofmann S, Mittal M, Fuchs B, Sommer N, et al. Heme oxygenase-2 and large-conductance Ca2+-activated K+ channels: lung vascular effects of hypoxia. Am J Respir Crit Care Med. 2009;180:353-64 pubmed publisher
    ..It is demonstrated that neither deletion of HO-2 nor BK channels affect acute, sustained, and chronic vascular responses to alveolar hypoxia in the lung. ..
  32. 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
  33. Li J, Al Khalili O, Ramosevac S, Eaton D, Denson D. Protein-protein interaction between cPLA2 and splice variants of alpha-subunit of BK channels. Am J Physiol Cell Physiol. 2010;298:C251-62 pubmed publisher
  34. Rosenfeld C, Liu X, Despain K. Pregnancy modifies the large conductance Ca2+-activated K+ channel and cGMP-dependent signaling pathway in uterine vascular smooth muscle. Am J Physiol Heart Circ Physiol. 2009;296:H1878-87 pubmed publisher
  35. Gore V, Ma V, Yin R, Ligutti J, Immke D, Doherty E, et al. Structure-activity relationship (SAR) investigations of tetrahydroquinolines as BKCa agonists. Bioorg Med Chem Lett. 2010;20:3573-8 pubmed publisher
    ..An example from this class of BKCa agonists was shown to depress the spontaneous neuronal discharges in an electrophysiological model of migraine. ..
  36. Yi L, Morgan J, Ragsdale S. Identification of a thiol/disulfide redox switch in the human BK channel that controls its affinity for heme and CO. J Biol Chem. 2010;285:20117-27 pubmed publisher
  37. Korovkina V, Stamnes S, Brainard A, England S. Nardilysin convertase regulates the function of the maxi-K channel isoform mK44 in human myometrium. Am J Physiol Cell Physiol. 2009;296:C433-40 pubmed publisher
    ..Overall, our data indicate that, in human myometrium, nardilysin convertase and mK44 channels are a part of the molecular mechanism that regulates the excitability of smooth muscle cells. ..
  38. Liu B, Gan L, Sun X, Zhu Y, Tong Z, Xu H, et al. Enhancement of BK(Ca) channel activity induced by hydrogen peroxide: involvement of lipid phosphatase activity of PTEN. Biochim Biophys Acta. 2009;1788:2174-82 pubmed publisher
    ..These findings may elucidate a new mechanism for H(2)O(2)-induced BK(Ca) channel activation and provide some evidences for the role of PTEN on vasodilation induced by H(2)O(2). ..
  39. Holtzclaw J, Grimm P, Sansom S. Intercalated cell BK-alpha/beta4 channels modulate sodium and potassium handling during potassium adaptation. J Am Soc Nephrol. 2010;21:634-45 pubmed publisher
    ..These changes streamline flow across the principal cells, producing gradients more favorable for potassium secretion and less favorable for sodium reabsorption. ..
  40. Ningaraj N, Sankpal U, Khaitan D, Meister E, Vats T. Modulation of KCa channels increases anticancer drug delivery to brain tumors and prolongs survival in xenograft model. Cancer Biol Ther. 2009;8:1924-33 pubmed
    ..A clinical outcome of this research is the discovery of a novel drug delivery system that circumvents the BBB/BTB to benefit brain tumor patients. ..
  41. Borbouse L, Dick G, Payne G, Berwick Z, Neeb Z, Alloosh M, et al. Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation. Am J Physiol Heart Circ Physiol. 2010;298:H1182-9 pubmed publisher
    ..These data indicate that the metabolic syndrome impairs coronary vasodilation in response to cardiac ischemia via reductions in the contribution of K(+) channels to reactive hyperemia. ..
  42. Asano S, Tune J, Dick G. Bisphenol A activates Maxi-K (K(Ca)1.1) channels in coronary smooth muscle. Br J Pharmacol. 2010;160:160-70 pubmed publisher
    ..Our data indicate that BPA increased the activity of Maxi-K channels and may represent a basis for some potential toxicological effects. ..
  43. Bentzen B, Andersen R, Olesen S, Grunnet M, Nardi A. Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo. Naunyn Schmiedebergs Arch Pharmacol. 2010;381:271-83 pubmed publisher
    ..1 channels, and we believe these novel tools may constitute a valuable addition to understanding the functional role of KCa1.1 channels under physiological and pathophysiological conditions. ..
  44. Unnerståle S, Lind J, Papadopoulos E, Mäler L. Solution structure of the HsapBK K+ channel voltage-sensor paddle sequence. Biochemistry. 2009;48:5813-21 pubmed publisher
    ..Similarities in the structure of the S3b-S4 fragment in BK and K(v) channels as well as important differences are seen, which may be important for explaining the details in paddle movement within a bilayer. ..
  45. Li J, Deng C, Gao F, Cheng J, Yu Z, Liu L, et al. Coexpression and characterization of the human large-conductance Ca(2+)-activated K (+) channel alpha + beta1 subunits in HEK293 cells. Mol Cell Biochem. 2009;331:117-26 pubmed publisher
  46. Tian L, McClafferty H, Jeffries O, Shipston M. Multiple palmitoyltransferases are required for palmitoylation-dependent regulation of large conductance calcium- and voltage-activated potassium channels. J Biol Chem. 2010;285:23954-62 pubmed publisher
    ..Finally, our approach may prove useful in elucidating the specificity of DHHC palmitoylation of intracellular domains of other ion channels and transmembrane proteins. ..
  47. Gao L, Cong B, Zhang L, Ni X. Expression of the calcium-activated potassium channel in upper and lower segment human myometrium during pregnancy and parturition. Reprod Biol Endocrinol. 2009;7:27 pubmed publisher
    ..Our results suggest that expression of BKCa alpha- and beta-subunit in pregnant myometrium is reduced during labour, which is consistent with the myometrial activity at the onset of parturition. ..
  48. Traut M, Berg D, Berg U, Mayerhofer A, Kunz L. Identification and characterization of Ca2+-activated K+ channels in granulosa cells of the human ovary. Reprod Biol Endocrinol. 2009;7:28 pubmed publisher
    ..g. acetylcholine, ATP, dopamine). The knowledge of ovarian K(Ca) channel properties and functions should help to understand the link between endocrine and paracrine/autocrine control in the human ovary. ..
  49. Wang Q, Kalogeris T, Wang M, Jones A, Korthuis R. Antecedent ethanol attenuates cerebral ischemia/reperfusion-induced leukocyte-endothelial adhesive interactions and delayed neuronal death: role of large conductance, Ca2+-activated K+ channels. Microcirculation. 2010;17:427-38 pubmed publisher
    ..Our results support a role for BK(Ca) channel activation in the neuroprotective effects of EtOH-PC in cerebral I/R. ..
  50. Köhler R, Kaistha B, Wulff H. Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease. Expert Opin Ther Targets. 2010;14:143-55 pubmed publisher
    ..Additional efforts are required to optimize these compounds and to validate them as cardiovascular-protective drugs. ..
  51. Albarwani S, Al Siyabi S, Baomar H, Hassan M. Exercise training attenuates ageing-induced BKCa channel downregulation in rat coronary arteries. Exp Physiol. 2010;95:746-55 pubmed publisher
    ..We conclude that low-intensity ET may be beneficial in restoring age-related decline in coronary vasodilatory properties mediated by BK(Ca) channels. ..
  52. Chang S, Gomes C, Hypolite J, Marx J, Alanzi J, Zderic S, et al. Detrusor overactivity is associated with downregulation of large-conductance calcium- and voltage-activated potassium channel protein. Am J Physiol Renal Physiol. 2010;298:F1416-23 pubmed publisher
    ..Furthermore, downregulation of the BK channel may contribute to DO by increasing the basal level of MLC(20) phosphorylation. ..
  53. Khaitan D, Sankpal U, Weksler B, Meister E, Romero I, Couraud P, et al. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain. BMC Cancer. 2009;9:258 pubmed publisher
    ..This distinction would in turn allow for the appropriate and efficient application of effective treatments while sparing patients with low risk for metastasis from the toxic side effects of chemotherapy. ..