calcium activated potassium channels


Summary: Potassium channels whose activation is dependent on intracellular calcium concentrations.

Top Publications

  1. Krishnamoorthy G, Shi J, Sept D, Cui J. The NH2 terminus of RCK1 domain regulates Ca2+-dependent BK(Ca) channel gating. J Gen Physiol. 2005;126:227-41 pubmed
  2. Chakrapani S, Perozo E. How to gate an ion channel: lessons from MthK. Nat Struct Mol Biol. 2007;14:180-2 pubmed
  3. Kuo M, Baker K, Wong L, Choe S. Dynamic oligomeric conversions of the cytoplasmic RCK domains mediate MthK potassium channel activity. Proc Natl Acad Sci U S A. 2007;104:2151-6 pubmed publisher
  4. Ye S, Li Y, Chen L, Jiang Y. Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of K+ channels. Cell. 2006;126:1161-73 pubmed publisher
    ..Our findings, along with the previously determined open MthK structure, allow us to elucidate the ligand gating mechanism of RCK-regulated K(+) channels...
  5. Heinen A, Camara A, Aldakkak M, Rhodes S, Riess M, Stowe D. Mitochondrial Ca2+-induced K+ influx increases respiration and enhances ROS production while maintaining membrane potential. Am J Physiol Cell Physiol. 2007;292:C148-56 pubmed
    ..We propose that mild matrix K(+) influx during states 2 and 4 increases mitochondrial respiration while maintaining DeltaPsi(m); this allows singlet electron uptake by O(2) and ROS generation. ..
  6. Parfenova L, Crane B, Rothberg B. Modulation of MthK potassium channel activity at the intracellular entrance to the pore. J Biol Chem. 2006;281:21131-8 pubmed
    ..Our results suggest that the small, hydrophobic alanine side chain at the K(+) channel bundle crossing may generate an intrinsically stable structure, which in turn shifts the closed-to-open-state equilibrium toward the closed state. ..
  7. Ledoux J, Werner M, Brayden J, Nelson M. Calcium-activated potassium channels and the regulation of vascular tone. Physiology (Bethesda). 2006;21:69-78 pubmed
    ..These differential calcium signals and targets represent multilayered opportunities for prevention and/or treatment of vascular dysfunctions. ..
  8. Heinen A, Huhn R, Smeele K, Zuurbier C, Schlack W, Preckel B, et al. Helium-induced preconditioning in young and old rat heart: impact of mitochondrial Ca(2+) -sensitive potassium channel activation. Anesthesiology. 2008;109:830-6 pubmed publisher
    ..75 +/- 0.05; not significant vs. Con). Helium causes mitochondrial uncoupling and induces preconditioning in young rats via Ca(2+) -sensitive potassium channel activation. However, these effects are lost in aged rats. ..
  9. Li Y, Berke I, Chen L, Jiang Y. Gating and inward rectifying properties of the MthK K+ channel with and without the gating ring. J Gen Physiol. 2007;129:109-20 pubmed

More Information


  1. Absi M, Burnham M, Weston A, Harno E, Rogers M, Edwards G. Effects of methyl beta-cyclodextrin on EDHF responses in pig and rat arteries; association between SK(Ca) channels and caveolin-rich domains. Br J Pharmacol. 2007;151:332-40 pubmed
    ..These studies reveal cellular organisation as a further complexity in the EDHF pathway signalling cascade. ..
  2. Park W, Son Y, Kim N, Youm J, Warda M, Ko J, et al. Direct modulation of Ca(2+)-activated K(+) current by H-89 in rabbit coronary arterial smooth muscle cells. Vascul Pharmacol. 2007;46:105-13 pubmed
    ..These findings suggest that H-89 increases the BK(Ca) current independently of PKA. ..
  3. Kim H, Lim H, Rho S, Eom S, Park C. Hydrophobic interface between two regulators of K+ conductance domains critical for calcium-dependent activation of large conductance Ca2+-activated K+ channels. J Biol Chem. 2006;281:38573-81 pubmed
    ..The hydrophobic interaction appears to be critical for the Ca(2+)-dependent gating of the large conductance Ca(2+)-activated K(+) channel. ..
  4. Gaspar T, Katakam P, Snipes J, Kis B, Domoki F, Bari F, et al. Delayed neuronal preconditioning by NS1619 is independent of calcium activated potassium channels. J Neurochem. 2008;105:1115-28 pubmed publisher
    ..However, the neuroprotective effect seems to be independent of cell membrane and mitochondrial BK(Ca) channels. Rather it is the consequence of ROS generation, activation of the PI3K pathway, and inhibition of caspase activation. ..
  5. Morrow J, Zakharov S, Liu G, Yang L, Sok A, Marx S. Defining the BK channel domains required for beta1-subunit modulation. Proc Natl Acad Sci U S A. 2006;103:5096-101 pubmed
    ..Although the functional interaction of alpha and beta1 requires the N-terminal tail of alpha, the physical association requires the S1, S2, and S3 transmembrane helices of alpha. ..
  6. Li W, Aldrich R. Unique inner pore properties of BK channels revealed by quaternary ammonium block. J Gen Physiol. 2004;124:43-57 pubmed
    ..These features could potentially contribute to the large conductance of BK channels. ..
  7. Xia X, Zhang X, Lingle C. Ligand-dependent activation of Slo family channels is defined by interchangeable cytosolic domains. J Neurosci. 2004;24:5585-91 pubmed
    ..Thus, ligand-specific regulation is defined by interchangeable cytosolic regulatory modules. ..
  8. Wang X, Yin C, Xi L, Kukreja R. Opening of Ca2+-activated K+ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice. Am J Physiol Heart Circ Physiol. 2004;287:H2070-7 pubmed
    ..We conclude that opening of KCa channels leads to both early and delayed preconditioning effects through a mechanism that is independent of nitric oxide. ..
  9. Cao C, Xia Q, Gao Q, Chen M, Wong T. Calcium-activated potassium channel triggers cardioprotection of ischemic preconditioning. J Pharmacol Exp Ther. 2005;312:644-50 pubmed
    ..In conclusion, the study provides evidence that the K(Ca) channel triggers cardioprotection of IPC, which involves mPTP. ..
  10. Sato T, Saito T, Saegusa N, Nakaya H. Mitochondrial Ca2+-activated K+ channels in cardiac myocytes: a mechanism of the cardioprotective effect and modulation by protein kinase A. Circulation. 2005;111:198-203 pubmed
    ..Our study further indicates that mitoK(Ca) channel activation confers cardioprotection in a manner similar to but independent of mitoK(ATP) channel activation. ..
  11. Sausbier M, Hu H, Arntz C, Feil S, Kamm S, Adelsberger H, et al. Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2+-activated K+ channel deficiency. Proc Natl Acad Sci U S A. 2004;101:9474-8 pubmed
    ..These results identify previously unknown roles of potassium channels in mammalian cerebellar function and motor control. In addition, they provide a previously undescribed animal model of cerebellar ataxia. ..
  12. Williams S, Wootton P, Mason H, Bould J, Iles D, Riccardi D, et al. Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science. 2004;306:2093-7 pubmed
    ..Furthermore, carotid body cells demonstrated HO-2-dependent hypoxic BK channel inhibition, which indicates that HO-2 is an oxygen sensor that controls channel activity during oxygen deprivation. ..
  13. Tanaka Y, Koike K, Toro L. MaxiK channel roles in blood vessel relaxations induced by endothelium-derived relaxing factors and their molecular mechanisms. J Smooth Muscle Res. 2004;40:125-53 pubmed
  14. Zhang G, Horrigan F. Cysteine modification alters voltage- and Ca(2+)-dependent gating of large conductance (BK) potassium channels. J Gen Physiol. 2005;125:213-36 pubmed
    ..C430A did not eliminate effects of MTSET on apparent Ca2+ affinity. However an additional mutation, C615S, in the Haem binding site reduced the effects of MTSET, consistent with a role for this region in Ca2+ binding. ..
  15. Orio P, Latorre R. Differential effects of beta 1 and beta 2 subunits on BK channel activity. J Gen Physiol. 2005;125:395-411 pubmed
    ..All allosteric coupling factors need to be increased in order to explain the observed effects when the alpha subunit is coexpressed with the beta2IR subunit. ..
  16. Weston A, Feletou M, Vanhoutte P, Falck J, Campbell W, Edwards G. Bradykinin-induced, endothelium-dependent responses in porcine coronary arteries: involvement of potassium channel activation and epoxyeicosatrienoic acids. Br J Pharmacol. 2005;145:775-84 pubmed
    ..These open endothelial IK(Ca) and SK(Ca) channels and also activate large-conductance calcium-sensitive K+ channels (BK(Ca)) on the surrounding myocytes. ..
  17. Cao C, Chen M, Wong T. The K(Ca) channel as a trigger for the cardioprotection induced by kappa-opioid receptor stimulation -- its relationship with protein kinase C. Br J Pharmacol. 2005;145:984-91 pubmed
    ..In conclusion, the high-conductance K(Ca) channel triggers cardioprotection induced by kappa-OR stimulation that involves inhibition of MPTP opening. The K(Ca) channel is located downstream of PKC. ..
  18. Meredith A, Thorneloe K, Werner M, Nelson M, Aldrich R. Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel. J Biol Chem. 2004;279:36746-52 pubmed
    ..These results reveal a central role for BK channels in urinary bladder function and indicate that BK channel dysfunction leads to overactive bladder and urinary incontinence. ..
  19. Du W, Bautista J, Yang H, Diez Sampedro A, You S, Wang L, et al. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet. 2005;37:733-8 pubmed
  20. Lu T, Wang X, He T, Zhou W, Kaduce T, Katusic Z, et al. Impaired arachidonic acid-mediated activation of large-conductance Ca2+-activated K+ channels in coronary arterial smooth muscle cells in Zucker Diabetic Fatty rats. Diabetes. 2005;54:2155-63 pubmed
    ..We conclude that PGI2 is the major AA metabolite in lean coronaries, and AA-mediated BK channel activation is impaired in ZDF coronaries due to reduced PGIS activity. ..
  21. Horrigan F, Heinemann S, Hoshi T. Heme regulates allosteric activation of the Slo1 BK channel. J Gen Physiol. 2005;126:7-21 pubmed
    ..To account for these effects, we consider the possibility that heme binding alters the structure of the RCK gating ring and thereby disrupts both Ca(2+)- and voltage-dependent gating as well as intrinsic stability of the open state. ..
  22. Shintani Y, Node K, Asanuma H, Sanada S, Takashima S, Asano Y, et al. Opening of Ca2+-activated K+ channels is involved in ischemic preconditioning in canine hearts. J Mol Cell Cardiol. 2004;37:1213-8 pubmed
    ..0 +/- 4.1%). Thus, we conclude that the opening of K(Ca) channel is involved in early trigger phase of the molecular mechanism of IP. ..
  23. Zeng X, Xia X, Lingle C. Divalent cation sensitivity of BK channel activation supports the existence of three distinct binding sites. J Gen Physiol. 2005;125:273-86 pubmed
    ..The major kinetic effect of the E399-related low affinity mechanism is to slow deactivation at mM Mg2+ or Ca2+. The results support the view that three distinct divalent-cation binding sites mediate regulation of BK channels. ..
  24. Pyott S, Glowatzki E, Trimmer J, Aldrich R. Extrasynaptic localization of inactivating calcium-activated potassium channels in mouse inner hair cells. J Neurosci. 2004;24:9469-74 pubmed
    ..These results indicate a novel function of BK channels in mammalian inner hair cells and provide a framework for future research. ..
  25. Solinas S, Maex R, De Schutter E. Dendritic amplification of inhibitory postsynaptic potentials in a model Purkinje cell. Eur J Neurosci. 2006;23:1207-18 pubmed
  26. Fakler B, Adelman J. Control of K(Ca) channels by calcium nano/microdomains. Neuron. 2008;59:873-81 pubmed publisher
    ..The results may serve as a model for other processes operated by local Ca(2+) domains. ..
  27. Funabashi K, Ohya S, Yamamura H, Hatano N, Muraki K, Giles W, et al. Accelerated Ca2+ entry by membrane hyperpolarization due to Ca2+-activated K+ channel activation in response to histamine in chondrocytes. Am J Physiol Cell Physiol. 2010;298:C786-97 pubmed publisher
    ..Thus, K(Ca) channels appear to play an important role in the positive feedback mechanism of [Ca(2+)](i) regulation in chondrocytes in the presence of articular cartilage inflammation. ..
  28. Wu D, Yuan J, Shi H, Hu Z. Palmatine, a protoberberine alkaloid, inhibits both Ca(2+)- and cAMP-activated Cl(-) secretion in isolated rat distal colon. Br J Pharmacol. 2008;153:1203-13 pubmed publisher
  29. Ambroisine M, Favre J, Oliviero P, Rodriguez C, Gao J, Thuillez C, et al. Aldosterone-induced coronary dysfunction in transgenic mice involves the calcium-activated potassium (BKCa) channels of vascular smooth muscle cells. Circulation. 2007;116:2435-43 pubmed
    ..The resulting alteration of relaxing responses may contribute to the deleterious effects of aldosterone in cardiovascular diseases. BKCa channels may therefore be useful therapeutic targets in cardiovascular diseases. ..
  30. Papazian D. S0, where is it?. J Gen Physiol. 2008;131:531-6 pubmed publisher
  31. Seong E, Cho H, Choi D, Joung Y, Lim C, Hur J, et al. Tomato plants overexpressing CaKR1 enhanced tolerance to salt and oxidative stress. Biochem Biophys Res Commun. 2007;363:983-8 pubmed
    ..These results suggest that CaKR1 is a key signaling molecule regulating plant antioxidant metabolism and defense responses. ..
  32. 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. ..
  33. Winter H, Ruttiger L, Müller M, Kuhn S, Brandt N, Zimmermann U, et al. Deafness in TRbeta mutants is caused by malformation of the tectorial membrane. J Neurosci. 2009;29:2581-7 pubmed publisher
  34. Kleger A, Seufferlein T, Malan D, Tischendorf M, Storch A, Wolheim A, et al. Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells. Circulation. 2010;122:1823-36 pubmed publisher
    ..This provides a novel strategy for the enrichment of cardiomyocytes and in particular, the generation of a specific subtype of cardiomyocytes, pacemaker-like cells, without genetic modification. ..
  35. Cuppoletti J, Malinowska D, Tewari K, Chakrabarti J, Ueno R. Cellular and molecular effects of unoprostone as a BK channel activator. Biochim Biophys Acta. 2007;1768:1083-92 pubmed
    ..These findings show that unoprostone has a distinctly different mechanism of action from latanoprost and PGF(2alpha). Whether unoprostone affects the BK channel directly or an unidentified signaling mechanism has not been determined. ..
  36. Sokoya E, You J, Chen J. DCEBIO-mediated dilations are attenuated in the female rat middle cerebral artery. J Vasc Res. 2007;44:169-74 pubmed
    ..Taken together, our data suggest that the transfer of hyperpolarization from the endothelium to the smooth muscle is impeded in the female rat MCA. ..
  37. Kusama N, Kajikuri J, Yamamoto T, Watanabe Y, Suzuki Y, Katsuya H, et al. Reduced hyperpolarization in endothelial cells of rabbit aortic valve following chronic nitroglycerine administration. Br J Pharmacol. 2005;146:487-97 pubmed
    ..It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced hyperpolarization in rabbit AVECs, possibly through chronic actions mediated by superoxide. ..
  38. Sacerdoti D, Bolognesi M, Di Pascoli M, Gatta A, McGiff J, Schwartzman M, et al. Rat mesenteric arterial dilator response to 11,12-epoxyeicosatrienoic acid is mediated by activating heme oxygenase. Am J Physiol Heart Circ Physiol. 2006;291:H1999-2002 pubmed
    ..We conclude that the rat mesenteric vasodilator action of 11,12-EET is mediated via an increase in HO activity and an activation of calcium-activated potassium channels. ..
  39. Toro L, Alioua A, Mahajan A, Nishimaru K, Zarei M, Stefani E. MaxiK, c-Src and vasoconstriction. J Muscle Res Cell Motil. 2004;25:616-7 pubmed
  40. Werner M, Zvara P, Meredith A, Aldrich R, Nelson M. Erectile dysfunction in mice lacking the large-conductance calcium-activated potassium (BK) channel. J Physiol. 2005;567:545-56 pubmed
    ..These results indicate that the BK channel has an important role in erectile function, and loss of the BK channel leads to erectile dysfunction. ..
  41. 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. ..
  42. Kuhlmann C, Schaefer C, Reinhold L, Tillmanns H, Erdogan A. Signalling mechanisms of SDF-induced endothelial cell proliferation and migration. Biochem Biophys Res Commun. 2005;335:1107-14 pubmed
    ..05). SDF-1-alpha increases endothelial proliferation and migration involving the activation of BK(Ca) and an increased production of NO. ..
  43. Rutherford M, Roberts W. Spikes and membrane potential oscillations in hair cells generate periodic afferent activity in the frog sacculus. J Neurosci. 2009;29:10025-37 pubmed publisher
    ..These results show that some frog saccular hair cells can generate spontaneous rhythmic activity that may drive periodic background activity in afferent axons. ..
  44. Sand A, Andersson E, Fried G. Nitric oxide donors mediate vasodilation in human placental arteries partly through a direct effect on potassium channels. Placenta. 2006;27:181-90 pubmed
    ..This effect profile is a unique feature of drugs acting by K(+) channel opening. The immunohistochemistry shows that BK(Ca) channels are located both in smooth muscle and in endothelium in placental arteries. ..
  45. Hu H, He M, Tao R, Sun H, Hu R, Zang W, et al. Characterization of ion channels in human preadipocytes. J Cell Physiol. 2009;218:427-35 pubmed publisher
  46. Tajima N, Schönherr K, Niedling S, Kaatz M, Kanno H, Schönherr R, et al. Ca2+-activated K+ channels in human melanoma cells are up-regulated by hypoxia involving hypoxia-inducible factor-1alpha and the von Hippel-Lindau protein. J Physiol. 2006;571:349-59 pubmed
    ..Thus, up-regulation of K(Ca) channels may be a novel mechanism by which HIFs can contribute to the malignant phenotype of human tumour cells. ..
  47. Sivan E, Kopell N. Oscillations and slow patterning in the antennal lobe. J Comput Neurosci. 2006;20:85-96 pubmed
    ..Consequently, the major effect of network inhibition is to redistribute the action potentials of the PNs from bursting to one action potential per cycle of the oscillations. ..
  48. Leuranguer V, Gluais P, Vanhoutte P, Verbeuren T, Feletou M. Openers of calcium-activated potassium channels and endothelium-dependent hyperpolarizations in the guinea pig carotid artery. Naunyn Schmiedebergs Arch Pharmacol. 2008;377:101-9 pubmed publisher
    ..By contrast, NS-309 is a reasonably potent and selective opener of both SK(Ca) and IK(Ca), and this compound mimics the endothelium-dependent hyperpolarizations to acetylcholine. ..
  49. Jung S, Kim K, Hille B, Nguyen T, Koh D. Pattern of Ca2+ increase determines the type of secretory mechanism activated in dog pancreatic duct epithelial cells. J Physiol. 2006;576:163-78 pubmed
    ..Thus, in addition to amplitude, the temporal pattern of [Ca(2+)](i) increases is an important mechanism for transducing extracellular stimuli into different physiological effects. ..
  50. Lancaster B, Hu H, Gibb B, Storm J. Kinetics of ion channel modulation by cAMP in rat hippocampal neurones. J Physiol. 2006;576:403-17 pubmed
    ..Maximal increases in firing were short-lasting (< 60 s) and gave way to moderately enhanced levels of spiking. The results demonstrate how the fidelity of phasic monoamine signalling can be preserved by the cAMP-PKA pathway. ..
  51. Kadekaro M, Su G, Chu R, Lei Y, Li J, Fang L. Effects of nitric oxide on expressions of nitrosocysteine and calcium-activated potassium channels in the supraoptic nuclei and neural lobe of dehydrated rats. Neurosci Lett. 2007;411:117-22 pubmed
    ..Our results indicate that NO signaling cascade may control the expression of BK channels through the regulation of nitrosocysteine in SON and neural lobe of rats during osmotic regulation. ..
  52. Gao Q, Yang B, Ye Z, Wang J, Bruce I, Xia Q. Opening the calcium-activated potassium channel participates in the cardioprotective effect of puerarin. Eur J Pharmacol. 2007;574:179-84 pubmed
    ..These findings indicate that puerarin protects the myocardium against ischemia and reperfusion injury via opening the calcium-activated potassium channel and activating protein kinase C. ..
  53. Pimentel A, Costa C, Carvalho L, Brandão R, Rangel B, Tano T, et al. The role of NO-cGMP pathway and potassium channels on the relaxation induced by clonidine in the rat mesenteric arterial bed. Vascul Pharmacol. 2007;46:353-9 pubmed
    ..Prostaglandins might participate in the vasodilator effect of clonidine when NO and EDHF mechanisms are blunted. ..