small conductance calcium activated potassium channels


Summary: A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.

Top Publications

  1. Zhang Q, Timofeyev V, Lu L, Li N, Singapuri A, Long M, et al. Functional roles of a Ca2+-activated K+ channel in atrioventricular nodes. Circ Res. 2008;102:465-71 pubmed
    ..The new insights may have important implications in providing novel drug targets for the modification of AVN conduction in the treatment of atrial arrhythmias. ..
  2. Lin M, Lujan R, Watanabe M, Adelman J, Maylie J. SK2 channel plasticity contributes to LTP at Schaffer collateral-CA1 synapses. Nat Neurosci. 2008;11:170-7 pubmed publisher
    ..Thus the increase in AMPARs and the decrease in SK2 channels combine to produce the increased EPSP underlying LTP. ..
  3. Corrêa S, Muller J, Collingridge G, Marrion N. Rapid endocytosis provides restricted somatic expression of a K+ channel in central neurons. J Cell Sci. 2009;122:4186-94 pubmed publisher
    ..The role of this novel motif is therefore not to directly target trafficking of the channel to subcellular compartments, but to regulate channel location by subjecting it to rapid clathrin-mediated endocytosis. ..
  4. Tuteja D, Rafizadeh S, Timofeyev V, Wang S, Zhang Z, Li N, et al. Cardiac small conductance Ca2+-activated K+ channel subunits form heteromultimers via the coiled-coil domains in the C termini of the channels. Circ Res. 2010;107:851-9 pubmed publisher
  5. Thorneloe K, Knorn A, Doetsch P, Lashinger E, Liu A, Bond C, et al. Small-conductance, Ca(2+) -activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1737-43 pubmed publisher
  6. Schultheiss N, Edgerton J, Jaeger D. Phase response curve analysis of a full morphological globus pallidus neuron model reveals distinct perisomatic and dendritic modes of synaptic integration. J Neurosci. 2010;30:2767-82 pubmed publisher
    ..These results highlight the need to consider different effects of perisomatic and dendritic inputs in the control of network behavior. ..
  7. Milkau M, Köhler R, de Wit C. Crucial importance of the endothelial K+ channel SK3 and connexin40 in arteriolar dilations during skeletal muscle contraction. FASEB J. 2010;24:3572-9 pubmed publisher
    ..The differential impact of SK3- and IK1-deficiency on dilations to distinct stimuli suggests stimulus-dependent activation of these endothelial channels. ..
  8. Brähler S, Kaistha A, Schmidt V, Wölfle S, Busch C, Kaistha B, et al. Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation. 2009;119:2323-32 pubmed publisher
    ..Endothelial K(Ca) channels may represent novel therapeutic targets for the treatment of hypertension. ..
  9. Ji H, Hougaard C, Herrik K, Strøbaek D, Christophersen P, Shepard P. Tuning the excitability of midbrain dopamine neurons by modulating the Ca2+ sensitivity of SK channels. Eur J Neurosci. 2009;29:1883-95 pubmed publisher

More Information


  1. Canavier C, Landry R. An increase in AMPA and a decrease in SK conductance increase burst firing by different mechanisms in a model of a dopamine neuron in vivo. J Neurophysiol. 2006;96:2549-63 pubmed
    ..Furthermore, blocking SK produced a longer burst with a greater intra-burst frequency in response to a simulated meaningful input, suggesting that reduction of this current may augment reward-related responses. ..
  2. Li W, Halling D, Hall A, Aldrich R. EF hands at the N-lobe of calmodulin are required for both SK channel gating and stable SK-calmodulin interaction. J Gen Physiol. 2009;134:281-93 pubmed publisher
    ..CaM (E/Q) can regulate Ca(2+)-dependent gating of SK channels in the presence of NS309, but with a lower apparent Ca(2+) affinity than WT CaM. ..
  3. 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...
  4. Chantome A, Girault A, Potier M, Collin C, Vaudin P, Pages J, et al. KCa2.3 channel-dependent hyperpolarization increases melanoma cell motility. Exp Cell Res. 2009;315:3620-30 pubmed publisher
    ..3 channel. Our findings reveal a previously unknown function of the KCa2.3 channel, and suggest that the KCa2.3 channel might be the only member of the Ca(2+)-activated K(+) channel family involved in melanoma cell motility pathways. ..
  5. Ellinor P, Lunetta K, Glazer N, Pfeufer A, Alonso A, Chung M, et al. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat Genet. 2010;42:240-4 pubmed publisher
    ..52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization. ..
  6. Hougaard C, Jensen M, Dale T, Miller D, Davies D, Eriksen B, et al. Selective activation of the SK1 subtype of human small-conductance Ca2+-activated K+ channels by 4-(2-methoxyphenylcarbamoyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (GW542573X) is dependent on serine 293 in the S5 segment. Mol Pharmacol. 2009;76:569-78 pubmed publisher
  7. Taranda J, Ballestero J, Hiel H, de Souza F, Wedemeyer C, Gómez Casati M, et al. Constitutive expression of the alpha10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing. J Assoc Res Otolaryngol. 2009;10:397-406 pubmed publisher
    ..These results indicate that multiple features of the efferent postsynaptic complex to IHCs, in addition to the nAChR subunits, are down-regulated in synchrony after the onset of hearing, leading to lack of responses to ACh. ..
  8. Ishikawa M, Mu P, Moyer J, Wolf J, Quock R, Davies N, et al. Homeostatic synapse-driven membrane plasticity in nucleus accumbens neurons. J Neurosci. 2009;29:5820-31 pubmed publisher
    ..These results suggest that hSMP is a novel form of synapse-to-membrane homeostatic plasticity and dysregulation of hSMP may contribute to cocaine-induced cellular alterations in the NAc. ..
  9. Zhu J, Jia R, Xu L, Wu J, Wang Z, Wang S, et al. Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats. Asian J Androl. 2010;12:599-604 pubmed publisher
    ..05). Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats. ..
  10. Lamy C, Scuvee Moreau J, Dilly S, Liégeois J, Seutin V. The sigma agonist 1,3-di-o-tolyl-guanidine directly blocks SK channels in dopaminergic neurons and in cell lines. Eur J Pharmacol. 2010;641:23-8 pubmed publisher
    ..Other sigma receptor ligands had little or no effect. We conclude that DTG directly blocks SK channels. This pharmacological action may be important to consider in future experimental settings. ..
  11. Cipolla M, Smith J, Kohlmeyer M, Godfrey J. SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion. Stroke. 2009;40:1451-7 pubmed publisher
    ..The preservation of EDHF responsiveness of PA after ischemia and reperfusion suggests an important role for this vasodilator under conditions when NOS is inhibited. ..
  12. Shishido T, Sakai S, Tosaka T. T- and L-type calcium channels mediate alpha(1)-adrenoceptor-evoked contraction in the guinea-pig vas deferens. Neurourol Urodyn. 2009;28:447-54 pubmed publisher
    ..Neurourol. Urodynam. 28:447-454, 2009. (c) 2009 Wiley-Liss, Inc. ..
  13. Sheng J, Ella S, Davis M, Hill M, Braun A. Openers of SKCa and IKCa channels enhance agonist-evoked endothelial nitric oxide synthesis and arteriolar vasodilation. FASEB J. 2009;23:1138-45 pubmed publisher
  14. Kita M, Yunoki T, Takimoto K, Miyazato M, Kita K, de Groat W, et al. Effects of bladder outlet obstruction on properties of Ca2+-activated K+ channels in rat bladder. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1310-9 pubmed publisher
  15. Faber E. Functional interplay between NMDA receptors, SK channels and voltage-gated Ca2+ channels regulates synaptic excitability in the medial prefrontal cortex. J Physiol. 2010;588:1281-92 pubmed publisher
    ..These findings show that interactions between NMDA receptors, SK channels and voltage-gated calcium channels play a critical role in regulating excitatory synaptic transmission in layer 5 pyramidal neurons in the mPFC. ..
  16. Artinian L, Tornieri K, Zhong L, Baro D, Rehder V. Nitric oxide acts as a volume transmitter to modulate electrical properties of spontaneously firing neurons via apamin-sensitive potassium channels. J Neurosci. 2010;30:1699-711 pubmed publisher
  17. Dalsgaard T, Kroigaard C, Misfeldt M, Bek T, Simonsen U. Openers of small conductance calcium-activated potassium channels selectively enhance NO-mediated bradykinin vasodilatation in porcine retinal arterioles. Br J Pharmacol. 2010;160:1496-508 pubmed publisher
    ..These results imply that opening SK(Ca) channels improves endothelium-dependent relaxation and makes this channel a potential target for treatments aimed at restoring retinal blood flow. ..
  18. 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. ..
  19. Coulon P, Herr D, Kanyshkova T, Meuth P, Budde T, Pape H. Burst discharges in neurons of the thalamic reticular nucleus are shaped by calcium-induced calcium release. Cell Calcium. 2009;46:333-46 pubmed publisher
    ..We conclude that the activation of LVACC specifically causes CICR via RyR in neurons of the NRT, thereby adding a Ca2+-dependent intracellular route to the mechanisms determining rhythmic oscillatory bursting in this nucleus. ..
  20. Pierce S, England S. SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of the KCNN3 gene. Am J Physiol Endocrinol Metab. 2010;299:E640-6 pubmed publisher
    ..Overall, our findings indicate that Sp1 and Sp3 compete to regulate SK3 channel expression during pregnancy in response to stimulation by estrogen. ..
  21. Kasten M, Rudy B, Anderson M. Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N-type calcium channels. J Physiol. 2007;584:565-82 pubmed
  22. Lu L, Timofeyev V, Li N, Rafizadeh S, Singapuri A, Harris T, et al. Alpha-actinin2 cytoskeletal protein is required for the functional membrane localization of a Ca2+-activated K+ channel (SK2 channel). Proc Natl Acad Sci U S A. 2009;106:18402-7 pubmed publisher
    ..The importance of our findings may transcend the area of K(+) channels, given that similar cytoskeletal interaction and anchoring may be critical for the membrane localization of other ion channels in neurons and other excitable cells. ..
  23. 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. ..
  24. Nagy N, Szuts V, Horvath Z, Seprényi G, Farkas A, Acsai K, et al. Does small-conductance calcium-activated potassium channel contribute to cardiac repolarization?. J Mol Cell Cardiol. 2009;47:656-63 pubmed publisher
    ..These results clearly demonstrate that in rat, dog and human ventricular cells under normal physiological conditions--though present--SK2 channels are not active and do not contribute to action potential repolarization. ..
  25. Deister C, Chan C, Surmeier D, Wilson C. Calcium-activated SK channels influence voltage-gated ion channels to determine the precision of firing in globus pallidus neurons. J Neurosci. 2009;29:8452-61 pubmed publisher
    ..This change made the neuron more sensitive to intrinsically generated noise. In vivo, this change would also enhance the sensitivity of GP neurons to small synaptic inputs. ..
  26. Mayer C, Macklin W, Avishai N, Balan K, Wilson C, Miller M. Mutation in the myelin proteolipid protein gene alters BK and SK channel function in the caudal medulla. Respir Physiol Neurobiol. 2009;169:303-14 pubmed publisher
    ..These results provide evidence that Plp mutation specifically alters neuronal excitability through calcium-dependent potassium channels in nTS. ..
  27. Wang Z, Sun P, Xing W, Pan C, Lin D, Wang W. Decrease in dietary K intake stimulates the generation of superoxide anions in the kidney and inhibits K secretory channels in the CCD. Am J Physiol Renal Physiol. 2010;298:F1515-22 pubmed publisher
    ..We conclude that LK intake stimulates the generation of superoxide anion and related products and that MAPK and Src family PTK play a physiological role in inhibiting apical K channels in the principal cells in response to LK intake. ..
  28. Hopf F, Bowers M, Chang S, Chen B, Martin M, Seif T, et al. Reduced nucleus accumbens SK channel activity enhances alcohol seeking during abstinence. Neuron. 2010;65:682-94 pubmed publisher
    ..Thus, decreased NAcb core SK currents and increased excitability represents a critical mechanism that facilitates motivation to seek alcohol after abstinence. ..
  29. Dalsgaard T, Kroigaard C, Simonsen U. Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease?. Expert Opin Ther Targets. 2010;14:825-37 pubmed publisher
    ..Opening of SK and IK channels can increase both EDHF and NO-mediated vasodilatation. Therefore, openers of SK and IK channels may have the potential of improving endothelial cell function in cardiovascular disease. ..
  30. Jacobsen J, Redrobe J, Hansen H, Petersen S, Bond C, Adelman J, et al. Selective cognitive deficits and reduced hippocampal brain-derived neurotrophic factor mRNA expression in small-conductance calcium-activated K+ channel deficient mice. Neuroscience. 2009;163:73-81 pubmed publisher
    ..BDNF has been crucially implicated in many cognitive processes. Hence, the biological substrate for the cognitive impairments in T/T mice could conceivably entail reduced trophic support of the hippocampus. ..
  31. Lamy C, Goodchild S, Weatherall K, Jane D, Liégeois J, Seutin V, et al. Allosteric block of KCa2 channels by apamin. J Biol Chem. 2010;285:27067-77 pubmed publisher
    ..This multidisciplinary approach suggested that apamin does not behave as a classical pore blocker but blocks using an allosteric mechanism that is consistent with observed differences between binding affinity and potency of block. ..
  32. Stackman R, Bond C, Adelman J. Contextual memory deficits observed in mice overexpressing small conductance Ca2+-activated K+ type 2 (KCa2.2, SK2) channels are caused by an encoding deficit. Learn Mem. 2008;15:208-13 pubmed publisher
    ..These data support converging evidence that SK2 channels restrict the encoding of hippocampal memory. ..
  33. Levin S, Shamsutdinova A, Godukhin O. Apamin, a selective blocker of SK(Ca) channels, inhibits posthypoxic hyperexcitability but does not affect rapid hypoxic preconditioning in hippocampal CA1 pyramidal neurons in vitro. Neurosci Lett. 2010;484:35-8 pubmed publisher
    ..However, SK(Ca) channels, in contrast to the BK(Ca) channels, are not involved in the rapid hypoxic preconditioning in CA1 hippocampal region in vitro. ..
  34. Faber E. Functions and modulation of neuronal SK channels. Cell Biochem Biophys. 2009;55:127-39 pubmed publisher
    ..This article will discuss recent findings regarding the function and modulation of SK channels in central neurons. ..
  35. Clark B, Kurth Nelson Z, Newman E. Adenosine-evoked hyperpolarization of retinal ganglion cells is mediated by G-protein-coupled inwardly rectifying K+ and small conductance Ca2+-activated K+ channel activation. J Neurosci. 2009;29:11237-45 pubmed publisher
    ..The coactivation of GIRK and SK channels represents a novel mechanism of adenosine-mediated neuromodulation that could contribute to the regulation of retinal ganglion cell activity. ..
  36. Lin M, Lujan R, Watanabe M, Frerking M, Maylie J, Adelman J. Coupled activity-dependent trafficking of synaptic SK2 channels and AMPA receptors. J Neurosci. 2010;30:11726-34 pubmed publisher
  37. Kleiman Weiner M, Beenhakker M, Segal W, Huguenard J. Synergistic roles of GABAA receptors and SK channels in regulating thalamocortical oscillations. J Neurophysiol. 2009;102:203-13 pubmed publisher
    ..Finally, our results suggest that changes in the intrinsic properties of individual neurons and changes at the circuit level can robustly modulate these oscillations. ..
  38. Abdullaev I, Rudkouskaya A, Mongin A, Kuo Y. Calcium-activated potassium channels BK and IK1 are functionally expressed in human gliomas but do not regulate cell proliferation. PLoS ONE. 2010;5:e12304 pubmed publisher
    ..Taken together, these results suggest that Ca(2+)-activated K(+) channels do not play a critical role in proliferation of glioma cells and that the effects of pharmacological inhibitors occur through their off-target actions. ..
  39. Oliveira M, Skinner F, Arshadmansab M, Garcia I, Mello C, Knaus H, et al. Altered expression and function of small-conductance (SK) Ca(2+)-activated K+ channels in pilocarpine-treated epileptic rats. Brain Res. 2010;1348:187-99 pubmed publisher
    ..These data indicate an abnormal expression of SK channels and a possible dysfunction of these channels in experimental MTLE. ..
  40. Pierce S, Kutschke W, Cabeza R, England S. In vivo measurement of intrauterine pressure by telemetry: a new approach for studying parturition in mouse models. Physiol Genomics. 2010;42:310-6 pubmed publisher
    ..The use of this technology will lead to important novel insights into changes in intrauterine pressure during the course of pregnancy. ..
  41. Rinaldi F, Botta A, Vallo L, Contino G, Morgante A, Iraci R, et al. Analysis of Single Nucleotide Polymorphisms (SNPs) of the small-conductance calcium activated potassium channel (SK3) gene as genetic modifier of the cardiac phenotype in myotonic dystrophy type 1 patients. Acta Myol. 2008;27:82-9 pubmed
    ..These findings suggest that modifier genes, other than SK3, should be identified in order to explain the cardiac phenotypic variability among DM1 patients. ..
  42. Schlichter L, Kaushal V, Moxon Emre I, Sivagnanam V, Vincent C. The Ca2+ activated SK3 channel is expressed in microglia in the rat striatum and contributes to microglia-mediated neurotoxicity in vitro. J Neuroinflammation. 2010;7:4 pubmed publisher
    ..Moreover, its roles in microglia must be considered when targeting this channel for CNS diseases, disorders and reducing neuron hyper-excitability. ..
  43. Lee A, Campbell L, Sapolsky R. Neighbor effects of neurons bearing protective transgenes. Brain Res. 2010;1339:70-5 pubmed publisher
    ..We also characterized the necessity for cell-cell contact for these effects. These phenomena may have broad implications for the efficacy of gene overexpression strategies in the CNS. ..
  44. Potier M, Tran T, Chantome A, Girault A, Joulin V, Bougnoux P, et al. Altered SK3/KCa2.3-mediated migration in adenomatous polyposis coli (Apc) mutated mouse colon epithelial cells. Biochem Biophys Res Commun. 2010;397:42-7 pubmed publisher
    ..3 channel mediated-cell migration. Our findings reveal a previously unknown function of the SK3/KCa2.3 channel in epithelial colonic cells, and suggest that Apc is a powerful regulator SK3/KCa2.3 channel. ..
  45. Dalsgaard T, Kroigaard C, Bek T, Simonsen U. Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles. Invest Ophthalmol Vis Sci. 2009;50:3819-25 pubmed publisher
    ..Moreover, these findings suggest that SK(Ca) channels contribute to NO-mediated relaxation induced by bradykinin and NS309 and, hence, may play an important role in retinal arterial endothelial function. ..
  46. Gao Y, Balut C, Bailey M, Patino Lopez G, Shaw S, Devor D. Recycling of the Ca2+-activated K+ channel, KCa2.3, is dependent upon RME-1, Rab35/EPI64C, and an N-terminal domain. J Biol Chem. 2010;285:17938-53 pubmed publisher
    ..3 with Rab35 but significantly decreased the association with RME-1. These represent the first studies elucidating the mechanisms by which KCa2.3 is maintained at the plasma membrane. ..
  47. Sones W, Leblanc N, Greenwood I. Inhibition of vascular calcium-gated chloride currents by blockers of KCa1.1, but not by modulators of KCa2.1 or KCa2.3 channels. Br J Pharmacol. 2009;158:521-31 pubmed publisher
    ..1 blockers also reduce I(ClCa) considerably. However, the pharmacological overlap that exists between CaCCs and K(Ca)1.1 does not extend to the calcium-binding domain or to other calcium-gated K(+) channels. ..
  48. Jasmin L, Vit J, Bhargava A, Ohara P. Can satellite glial cells be therapeutic targets for pain control?. Neuron Glia Biol. 2010;6:63-71 pubmed publisher
    ..Taken together these data suggest that SGCs may play a role in the genesis or maintenance of pain and open a range of new possibilities for curing neuropathic pain. ..
  49. Pierce S, Kresowik J, Lamping K, England S. Overexpression of SK3 channels dampens uterine contractility to prevent preterm labor in mice. Biol Reprod. 2008;78:1058-63 pubmed publisher
    ..Our data indicate that SK3 channels must be downregulated for the gravid uterus to generate labor contractions sufficient for delivery in both term and preterm mice...
  50. Toporikova N, Chacron M. SK channels gate information processing in vivo by regulating an intrinsic bursting mechanism seen in vitro. J Neurophysiol. 2009;102:2273-87 pubmed publisher
    ..Our results show that ion channels located in dendrites can have a profound influence on the processing of sensory input by neurons in vivo through the modulation of an intrinsic bursting mechanism. ..
  51. Liu Y, Sellke E, Feng J, Clements R, Sodha N, Khabbaz K, et al. Calcium-activated potassium channels contribute to human skeletal muscle microvascular endothelial dysfunction related to cardiopulmonary bypass. Surgery. 2008;144:239-44 pubmed publisher
    ..CPB-associated microvascular dysfunction likely arises in part from impaired function of endothelial SK and IK channels in the peripheral microvasculature. ..
  52. 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
  53. Goodchild S, Lamy C, Seutin V, Marrion N. Inhibition of K(Ca)2.2 and K(Ca)2.3 channel currents by protonation of outer pore histidine residues. J Gen Physiol. 2009;134:295-308 pubmed publisher
    ..2 to an asparagine residue. These data suggest that local interactions involving the outer turret histidine residues are crucial to enable high conductance openings, with protonation inhibiting current by changing pore shape. ..