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Gene Review

Kcnma1  -  potassium large conductance calcium...

Mus musculus

Synonyms: 5730414M22Rik, BK channel, BK channel alpha subunit, BKCA alpha, BKCa, ...
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Disease relevance of Kcnma1


Psychiatry related information on Kcnma1


High impact information on Kcnma1

  • Here we show that targeted deletion of the gene for the beta1 subunit leads to a decrease in the calcium sensitivity of BK channels, a reduction in functional coupling of calcium sparks to BK channel activation, and increases in arterial tone and blood pressure [7].
  • Complementary DNAs (cDNAs) from mSlo, a gene encoding calcium-activated potassium channels, were isolated from mouse brain and skeletal muscle, sequenced, and expressed in Xenopus oocytes [8].
  • BK channel beta4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures [9].
  • Our results indicate that NT-3 stimulates BK channel activity in cortical neurons through a signaling pathway that involves Trk tyrosine kinase, phospholipase C, and protein dephosphorylation and is calcium-dependent [10].
  • During angiotensin II infusion, arterial smooth muscle BK channel function was decreased in wild type (WT) but not in NFATc3 null (NFATc3(-/-)) mice [11].

Biological context of Kcnma1

  • Mouse Kcnma1 transcripts, 5' and 3' ESTs, and genomic sequences were examined for the utilization of alternative splicing in the mouse transcriptome [12].
  • Here we demonstrated that alternative splicing at site of splicing C2 in the mouse BK channel C terminus generates five distinct splice variants: ZERO, e20, e21(STREX), e22, and a novel variant deltae23 [13].
  • These results suggest that Slo channels comprise a multigene family, defined by a combination of sensitivity to voltage and a variety of intracellular factors [14].
  • Thus alternative pre-mRNA splicing from a single site of splicing provides a mechanism to generate a physiologically diverse complement of BK channel alpha-subunits that differ dramatically in their tissue distribution, trafficking, and regulation [13].
  • Mutagenesis of the central two LZ1 d position leucines to alanine in the BK channel also eliminated regulation by endogenous PKA in HEK293 cells without altering the channel sensitivity to activation by voltage or by exogenous purified PKA [15].

Anatomical context of Kcnma1

  • Urinary bladder smooth muscle cells of Slo(-/-) mice lacked calcium- and voltage-activated BK currents, whereas local calcium transients ("calcium sparks") and voltage-dependent potassium currents were unaffected [2].
  • To confirm the genetic identity of the maxi-K channel and to probe its specific roles, we studied parotid glands in mice with the K(Ca)1.1 gene ablated [16].
  • The expression of Slo channels (alpha subunits of BK channels) was investigated in the developing mouse cochlea using a polyclonal antibody against the C-terminal part of the protein (residues 1098-1196) [17].
  • The first BK channel immunoreactivity was observed in the cochlea at E18, where it was localized within the cytoplasm of cells lining the area of the organ of Corti and the spiral ganglion [17].
  • 17beta-Estradiol upregulates distinct maxi-K channel transcripts in mouse uterus [18].

Associations of Kcnma1 with chemical compounds

  • Thus LZ1 is required for the association and regulation of mammalian BK channels by PKA, and other putative leucine zippers in the BK channel protein may provide anchoring for other regulatory enzyme complexes [15].
  • BK channels localize to the luminal membrane of crypt, and reverse transcription-PCR results confirm the expression of the BK channel alpha-subunit in isolated distal colonic crypts [19].
  • Like Slo1 subunits responsible for the Ca(2+) and voltage-activated BK-type channel, the Slo3 alpha subunit contains a pore module with homology to voltage-gated K(+) channels and also an extensive cytosolic C terminus thought to be responsible for ligand dependence [20].
  • Myometrial maxi-K channel beta1 subunit modulation during pregnancy and after 17beta-estradiol stimulation [21].
  • We conclude that activation of calcineurin and NFATc3 during sustained angiotensin II signaling down-regulates the expression of the beta1 subunit of the BK channel, which in turn contributes to arterial dysfunction and the development of hypertension [11].

Regulatory relationships of Kcnma1

  • These data suggest that IK1 channels inhibit maxi-K channel activity via a direct, membrane-delimited interaction between the channel proteins [22].

Other interactions of Kcnma1


Analytical, diagnostic and therapeutic context of Kcnma1


  1. A cysteine-rich motif confers hypoxia sensitivity to mammalian large conductance voltage- and Ca-activated K (BK) channel alpha-subunits. McCartney, C.E., McClafferty, H., Huibant, J.M., Rowan, E.G., Shipston, M.J., Rowe, I.C. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel. Meredith, A.L., Thorneloe, K.S., Werner, M.E., Nelson, M.T., Aldrich, R.W. J. Biol. Chem. (2004) [Pubmed]
  3. Cochlear Function in Mice Lacking the BK Channel {alpha}, beta1, or beta4 Subunits. Pyott, S.J., Meredith, A.L., Fodor, A.A., Vázquez, A.E., Yamoah, E.N., Aldrich, R.W. J. Biol. Chem. (2007) [Pubmed]
  4. Modulation of big K+ channel activity by ryanodine receptors and L-type Ca2+ channels in neurons. Chavis, P., Ango, F., Michel, J.M., Bockaert, J., Fagni, L. Eur. J. Neurosci. (1998) [Pubmed]
  5. Cardioprotective effects of estradiol include the activation of large-conductance Ca(2+)-activated K(+) channels in cardiac mitochondria. Ohya, S., Kuwata, Y., Sakamoto, K., Muraki, K., Imaizumi, Y. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  6. Erectile dysfunction in mice lacking the large-conductance calcium-activated potassium (BK) channel. Werner, M.E., Zvara, P., Meredith, A.L., Aldrich, R.W., Nelson, M.T. J. Physiol. (Lond.) (2005) [Pubmed]
  7. Vasoregulation by the beta1 subunit of the calcium-activated potassium channel. Brenner, R., Peréz, G.J., Bonev, A.D., Eckman, D.M., Kosek, J.C., Wiler, S.W., Patterson, A.J., Nelson, M.T., Aldrich, R.W. Nature (2000) [Pubmed]
  8. mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels. Butler, A., Tsunoda, S., McCobb, D.P., Wei, A., Salkoff, L. Science (1993) [Pubmed]
  9. BK channel beta4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures. Brenner, R., Chen, Q.H., Vilaythong, A., Toney, G.M., Noebels, J.L., Aldrich, R.W. Nat. Neurosci. (2005) [Pubmed]
  10. Activation of calcium-dependent potassium channels in mouse [correction of rat] brain neurons by neurotrophin-3 and nerve growth factor. Holm, N.R., Christophersen, P., Olesen, S.P., Gammeltoft, S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  11. Activation of NFATc3 Down-regulates the beta1 Subunit of Large Conductance, Calcium-activated K+ Channels in Arterial Smooth Muscle and Contributes to Hypertension. Nieves-Cintrón, M., Amberg, G.C., Nichols, C.B., Molkentin, J.D., Santana, L.F. J. Biol. Chem. (2007) [Pubmed]
  12. Diversity of Ca(2+)-activated K(+) channel transcripts in inner ear hair cells. Beisel, K.W., Rocha-Sanchez, S.M., Ziegenbein, S.J., Morris, K.A., Kai, C., Kawai, J., Carninci, P., Hayashizaki, Y., Davis, R.L. Gene (2007) [Pubmed]
  13. Functionally diverse complement of large conductance calcium- and voltage-activated potassium channel (BK) alpha-subunits generated from a single site of splicing. Chen, L., Tian, L., MacDonald, S.H., McClafferty, H., Hammond, M.S., Huibant, J.M., Ruth, P., Knaus, H.G., Shipston, M.J. J. Biol. Chem. (2005) [Pubmed]
  14. Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes. Schreiber, M., Wei, A., Yuan, A., Gaut, J., Saito, M., Salkoff, L. J. Biol. Chem. (1998) [Pubmed]
  15. Leucine zipper domain targets cAMP-dependent protein kinase to mammalian BK channels. Tian, L., Coghill, L.S., MacDonald, S.H., Armstrong, D.L., Shipston, M.J. J. Biol. Chem. (2003) [Pubmed]
  16. Molecular identification and physiological roles of parotid acinar cell maxi-k channels. Romanenko, V., Nakamoto, T., Srivastava, A., Melvin, J.E., Begenisich, T. J. Biol. Chem. (2006) [Pubmed]
  17. Localization and developmental expression of BK channels in mammalian cochlear hair cells. Hafidi, A., Beurg, M., Dulon, D. Neuroscience (2005) [Pubmed]
  18. 17beta-Estradiol upregulates distinct maxi-K channel transcripts in mouse uterus. Holdiman, A.J., Fergus, D.J., England, S.K. Mol. Cell. Endocrinol. (2002) [Pubmed]
  19. Distal Colonic K+ Secretion Occurs via BK Channels. Sausbier, M., Matos, J.E., Sausbier, U., Beranek, G., Arntz, C., Neuhuber, W., Ruth, P., Leipziger, J. J. Am. Soc. Nephrol. (2006) [Pubmed]
  20. Slo3 K+ Channels: Voltage and pH Dependence of Macroscopic Currents. Zhang, X., Zeng, X., Lingle, C.J. J. Gen. Physiol. (2006) [Pubmed]
  21. Myometrial maxi-K channel beta1 subunit modulation during pregnancy and after 17beta-estradiol stimulation. Benkusky, N.A., Korovkina, V.P., Brainard, A.M., England, S.K. FEBS Lett. (2002) [Pubmed]
  22. Membrane-delimited inhibition of maxi-K channel activity by the intermediate conductance Ca2+-activated K channel. Thompson, J., Begenisich, T. J. Gen. Physiol. (2006) [Pubmed]
  23. Glucocorticoids block protein kinase A inhibition of calcium-activated potassium channels. Shipston, M.J., Kelly, J.S., Antoni, F.A. J. Biol. Chem. (1996) [Pubmed]
  24. Ca(2+)-activated K(+) channels of the BK-type in the mouse brain. Sausbier, U., Sausbier, M., Sailer, C.A., Arntz, C., Knaus, H.G., Neuhuber, W., Ruth, P. Histochem. Cell Biol. (2006) [Pubmed]
  25. Molecular identification of Ca2+-activated K+ channels in parotid acinar cells. Nehrke, K., Quinn, C.C., Begenisich, T. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  26. BK channel beta1-subunit regulation of calcium handling and constriction in tracheal smooth muscle. Semenov, I., Wang, B., Herlihy, J.T., Brenner, R. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  27. State-dependent modulation of mSlo, a cloned calcium-dependent potassium channel. Müller, M., Madan, D., Levitan, I.B. Neuropharmacology (1996) [Pubmed]
  28. Extrasynaptic localization of inactivating calcium-activated potassium channels in mouse inner hair cells. Pyott, S.J., Glowatzki, E., Trimmer, J.S., Aldrich, R.W. J. Neurosci. (2004) [Pubmed]
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