Kcnmb1

Summary

Gene Symbol: Kcnmb1
Description: potassium large conductance calcium-activated channel, subfamily M, beta member 1
Alias: BKbeta1, calcium-activated potassium channel subunit beta-1, BK channel beta subunit, BK channel subunit beta-1, BKbeta, calcium-activated potassium channel subunit beta, calcium-activated potassium channel, subfamily M subunit beta-1, charybdotoxin receptor subunit beta-1, k(VCA)beta-1, maxi K channel subunit beta-1, slo-beta, slo-beta-1
Species: mouse
Products:     Kcnmb1

Top Publications

  1. Jiang Z, Wallner M, Meera P, Toro L. Human and rodent MaxiK channel beta-subunit genes: cloning and characterization. Genomics. 1999;55:57-67 pubmed
    ..We cloned and analyzed human and rodent genes for the modulatory beta subunit, KCNMB1. The human and mouse beta-subunit genes are approximately 11 and approximately 9 kb in length, respectively, and ..
  2. Plüger S, Faulhaber J, Furstenau M, Lohn M, Waldschutz R, Gollasch M, et al. Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca(2+) spark/STOC coupling and elevated blood pressure. Circ Res. 2000;87:E53-60 pubmed
    ..BK channels are composed of channel-forming BKalpha and auxiliary BKbeta1 subunits, which confer to BK channels an increased sensitivity for changes in membrane potential and Ca(2+)...
  3. Bautista L, Castro M, Lopez Barneo J, Castellano A. Hypoxia inducible factor-2alpha stabilization and maxi-K+ channel beta1-subunit gene repression by hypoxia in cardiac myocytes: role in preconditioning. Circ Res. 2009;104:1364-72 pubmed publisher
    ..We report here that beta(1) protein may interact with mitochondrial proteins and that the beta(1)-subunit gene (KCNMB1) is repressed by sustained hypoxia in dispersed cardiomyocytes as well as in heart intact tissue...
  4. Xu H, Wang Y, Garver H, Galligan J, Fink G. Vascular BK channel deficiency exacerbates organ damage and mortality in endotoxemic mice. J Cardiovasc Pharmacol. 2012;59:207-14 pubmed publisher
    ..Reduced vascular BK channel function does not protect against hypotension in the early stage of septic shock; in the later stage, smooth muscle BK channel deficiency enhances organ damage and mortality. ..
  5. Bugaj V, Sansom S, Wen D, Hatcher L, Stockand J, Mironova E. Flow-sensitive K+-coupled ATP secretion modulates activity of the epithelial Na+ channel in the distal nephron. J Biol Chem. 2012;287:38552-8 pubmed publisher
    ..Impaired sodium excretion resulting form loss of normal purinergic regulation of ENaC in BK-?4 null mice likely contributes to their elevated blood pressure. ..
  6. Lynch F, Withers S, Yao Z, Werner M, Edwards G, Weston A, et al. Perivascular adipose tissue-derived adiponectin activates BK(Ca) channels to induce anticontractile responses. Am J Physiol Heart Circ Physiol. 2013;304:H786-95 pubmed publisher
    ..PVAT releases adiponectin, which is an anticontractile factor. Its effect on vascular tone is mediated by activation of BKCa channels on vascular smooth muscle cells and adipocytes and by endothelial mechanisms. ..
  7. Nystoriak M, Nieves Cintrón M, Nygren P, Hinke S, Nichols C, Chen C, et al. AKAP150 contributes to enhanced vascular tone by facilitating large-conductance Ca2+-activated K+ channel remodeling in hyperglycemia and diabetes mellitus. Circ Res. 2014;114:607-15 pubmed publisher
    ..Our results support a model whereby subcellular anchoring of CaN by AKAP150 is a key molecular determinant of vascular BKCa channel remodeling, which contributes to vasoconstriction during diabetes mellitus. ..
  8. Yi F, Wang H, Chai Q, Wang X, Shen W, Willis M, et al. Regulation of large conductance Ca2+-activated K+ (BK) channel ?1 subunit expression by muscle RING finger protein 1 in diabetic vessels. J Biol Chem. 2014;289:10853-64 pubmed publisher
    ..Hence, our results provide the first evidence that the up-regulation of NF-?B-dependent MuRF1 expression is a novel mechanism that leads to BK channelopathy and vasculopathy in diabetes. ..
  9. Sachse G, Faulhaber J, Seniuk A, Ehmke H, Pongs O. Smooth muscle BK channel activity influences blood pressure independent of vascular tone in mice. J Physiol. 2014;592:2563-74 pubmed publisher
    ..We conclude that BK channel activity directly affects vascular tone but influences blood pressure independent of this effect via different pathways. ..

More Information

Publications47

  1. 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. ..
  2. 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. ..
  3. France M, Bhattarai Y, Galligan J, Xu H. Impaired propulsive motility in the distal but not proximal colon of BK channel ?1-subunit knockout mice. Neurogastroenterol Motil. 2012;24:e450-9 pubmed publisher
    ..BK channels play a prominent role in smooth muscle function only in the distal colon of mice. Defects in smooth muscle BK channel function disrupt colonic motility causing constipation. ..
  4. Dick G, Sanders K. (Xeno)estrogen sensitivity of smooth muscle BK channels conferred by the regulatory beta1 subunit: a study of beta1 knockout mice. J Biol Chem. 2001;276:44835-40 pubmed
    ..We demonstrate regulation of smooth muscle BK channels by physiological (steroid hormones) and pharmacological (chemotherapeutic) agents and reveal the critical role of the beta1 subunit in these responses in native myocytes. ..
  5. Seidel K, Derst C, Salzmann M, Höltje M, Priller J, Markgraf R, et al. Expression of the voltage- and Ca2+-dependent BK potassium channel subunits BK?1 and BK?4 in rodent astrocytes. Glia. 2011;59:893-902 pubmed publisher
    ..Thus, BK?4 expression in astrocytes likely participates in regulating astrocytic voltage gradients and maintaining K(+) homeostasis, hence enabling astrocytes to fulfill their complex regulatory influence on proper brain function. ..
  6. Pyott S, Meredith A, Fodor A, Vazquez A, Yamoah E, Aldrich R. Cochlear function in mice lacking the BK channel alpha, beta1, or beta4 subunits. J Biol Chem. 2007;282:3312-24 pubmed
    ..These findings reveal the fundamentally different contribution of BK channels to nonmammalian and mammalian hearing and suggest that BK channels should be considered a target in the prevention of noise-induced hearing loss. ..
  7. Wan E, Kushner J, Zakharov S, Nui X, Chudasama N, Kelly C, et al. Reduced vascular smooth muscle BK channel current underlies heart failure-induced vasoconstriction in mice. FASEB J. 2013;27:1859-67 pubmed publisher
    ..These findings identify electrical dysregulation within VSM, specifically the reduction of BK currents, as a key molecular mechanism sensitizing resistance vessels to pressure-induced vasoconstriction in systolic HF. ..
  8. Shelton E, Ector G, Galindo C, Hooper C, Brown N, Wilkerson I, et al. Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone. Physiol Genomics. 2014;46:457-66 pubmed publisher
    ..Ion channels that regulate DA tone, including BKCa channels, are promising targets. Specifically, BKCa channel agonists like NS1619 maintain DA patency even in the presence of O2 and may be clinically useful. ..
  9. Leo M, Zhai X, Muralidharan P, Kuruvilla K, Bulley S, Boop F, et al. Membrane depolarization activates BK channels through ROCK-mediated β1 subunit surface trafficking to limit vasoconstriction. Sci Signal. 2017;10: pubmed publisher
    ..Thus, membrane depolarization activates BK channels through stimulation of ROCK- and Rab11A-dependent trafficking of β1 subunits to the surface of arterial myocytes. ..
  10. Semenov I, Wang B, Herlihy J, Brenner R. BK channel ?1 subunits regulate airway contraction secondary to M2 muscarinic acetylcholine receptor mediated depolarization. J Physiol. 2011;589:1803-17 pubmed publisher
  11. Brenner R, Perez G, Bonev A, Eckman D, Kosek J, Wiler S, et al. Vasoregulation by the beta1 subunit of the calcium-activated potassium channel. Nature. 2000;407:870-6 pubmed
    ..The beta1 subunit of the BK channel, by tuning the channel's calcium sensitivity, is a key molecular component in translating calcium signals to the central physiological function of vasoregulation. ..
  12. Hagen B, Bayguinov O, Sanders K. Beta 1-subunits are required for regulation of coupling between Ca2+ transients and Ca2+-activated K+ (BK) channels by protein kinase C. Am J Physiol Cell Physiol. 2003;285:C1270-80 pubmed
    ..These data show that PKC-dependent regulation of coupling strength between Ca2+ transients and STOCs in colonic myocytes depends upon the interaction between alpha- and beta1-subunits. ..
  13. Ruttiger L, Sausbier M, Zimmermann U, Winter H, Braig C, Engel J, et al. Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BKbeta1-subunit leads to progressive hearing loss. Proc Natl Acad Sci U S A. 2004;101:12922-7 pubmed
    ..Analyzing the hearing function and cochlear phenotype of BK channel alpha-(BKalpha-/-) and beta1-subunit (BKbeta1-/-) knockout mice, we demonstrate normal hearing function and cochlear structure of BKbeta1-/- mice...
  14. Grimm P, Irsik D, Settles D, Holtzclaw J, Sansom S. Hypertension of Kcnmb1-/- is linked to deficient K secretion and aldosteronism. Proc Natl Acad Sci U S A. 2009;106:11800-5 pubmed publisher
    Mice lacking the beta1-subunit (gene, Kcnmb1; protein, BK-beta1) of the large Ca-activated K channel (BK) are hypertensive...
  15. Long X, Tharp D, Georger M, Slivano O, Lee M, Wamhoff B, et al. The smooth muscle cell-restricted KCNMB1 ion channel subunit is a direct transcriptional target of serum response factor and myocardin. J Biol Chem. 2009;284:33671-82 pubmed publisher
    ..Using several model systems, we demonstrate down-regulation of Kcnmb1 mRNA upon SMC phenotypic modulation in vitro and in vivo...
  16. Scornik F, Bucciero R, Wu Y, Selga E, Bosch Calero C, Brugada R, et al. DiBAC?(3) hits a "sweet spot" for the activation of arterial large-conductance Ca²?-activated potassium channels independently of the ??-subunit. Am J Physiol Heart Circ Physiol. 2013;304:H1471-82 pubmed publisher
    ..Arterial BK channel response to DiBAC?(3) varies across species and/or vascular beds. DiBAC?(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. ..
  17. Bukiya A, Vaithianathan T, Kuntamallappanavar G, Asuncion Chin M, Dopico A. Smooth muscle cholesterol enables BK ?1 subunit-mediated channel inhibition and subsequent vasoconstriction evoked by alcohol. Arterioscler Thromb Vasc Biol. 2011;31:2410-23 pubmed publisher
    ..VSMC cholesterol and BK ?1 are both required for ethanol inhibition of BK and the resulting cerebral artery constriction, with health-related implications for manipulating cholesterol levels in alcohol-induced cerebrovascular disease. ..
  18. Greenwood I, Miller L, Ohya S, Horowitz B. The large conductance potassium channel beta-subunit can interact with and modulate the functional properties of a calcium-activated chloride channel, CLCA1. J Biol Chem. 2002;277:22119-22 pubmed
    ..cells stably expressing CLCA1 with 500 nM Ca(2+) evoked a significantly larger current when the beta-subunit KCNMB1 was co-expressed...
  19. Lu T, Chai Q, Yu L, d Uscio L, Katusic Z, He T, et al. Reactive oxygen species signaling facilitates FOXO-3a/FBXO-dependent vascular BK channel ?1 subunit degradation in diabetic mice. Diabetes. 2012;61:1860-8 pubmed publisher
    ..Suppression of the FOXO-3a/FBXO pathway prevented vascular BK-?(1) degradation and protected coronary function in diabetes. ..
  20. PEREZ G. Dual effect of tamoxifen on arterial KCa channels does not depend on the presence of the beta1 subunit. J Biol Chem. 2005;280:21739-47 pubmed
    ..This dual effect of tamoxifen appears to be independent of the beta1 subunit. The molecular specificity of tamoxifen, or eventually other xenoestrogen derivatives, for the KCa channel beta1 subunit is uncertain. ..
  21. Loot A, Moneke I, Keserü B, Oelze M, Syzonenko T, Daiber A, et al. 11,12-EET stimulates the association of BK channel ? and ?(1) subunits in mitochondria to induce pulmonary vasoconstriction. PLoS ONE. 2012;7:e46065 pubmed publisher
    ..The 11,12-EET-induced activation of BK channels results in loss of the mitochondrial membrane potential and depolarization of the pulmonary artery smooth muscle cells. ..
  22. Bhattarai Y, Fried D, Gulbransen B, Kadrofske M, Fernandes R, Xu H, et al. High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon. Am J Physiol Gastrointest Liver Physiol. 2016;311:G210-20 pubmed publisher
    ..We conclude that HFD-induced obesity disrupts inhibitory neuromuscular transmission, SMC excitability, and colonic motility by promoting oxidative stress, loss of nitrergic neurons, and SMC BK channel dysfunction. ..
  23. Nehrke K, Quinn C, Begenisich T. Molecular identification of Ca2+-activated K+ channels in parotid acinar cells. Am J Physiol Cell Physiol. 2003;284:C535-46 pubmed
    ..RT-PCR analysis revealed the presence of two mSlo beta-subunits (Kcnmb1 and Kcnmb4) in parotid tissue...
  24. Pluznick J, Wei P, Carmines P, Sansom S. Renal fluid and electrolyte handling in BKCa-beta1-/- mice. Am J Physiol Renal Physiol. 2003;284:F1274-9 pubmed
  25. Pluznick J, Wei P, Grimm P, Sansom S. BK-{beta}1 subunit: immunolocalization in the mammalian connecting tubule and its role in the kaliuretic response to volume expansion. Am J Physiol Renal Physiol. 2005;288:F846-54 pubmed publisher
    ..These data show that the BK-beta1 accessory subunit is present in the CNT segment of the mammalian distal nephron and has a significant role in the kaliuretic response to increased urinary flow induced by volume expansion...
  26. Son Y, Chun W, Ahn Y, Kim K, Lee C, Kim J, et al. 7-Ketocholesterol induces the reduction of KCNMB1 in atherosclerotic blood vessels. Biochem Biophys Res Commun. 2015;457:324-7 pubmed publisher
    ..1-Subunit of BKCa channel (KCNMB1; MaxiKβ1) has been reported as a modulator of vascular flexibility...
  27. Fernández Mariño A, Porras González C, González Rodríguez P, Selent J, Pastor M, Ureña J, et al. Tungstate activates BK channels in a ? subunit- and Mg2+-dependent manner: relevance for arterial vasodilatation. Cardiovasc Res. 2012;95:29-38 pubmed publisher
    ..Tungstate activates BK channels in a ? subunit- and Mg(2+)-dependent manner and induces vasodilatation only in mouse arteries that express the BK ?(1) subunit. ..
  28. Semenov I, Wang B, Herlihy J, Brenner R. BK channel beta1-subunit regulation of calcium handling and constriction in tracheal smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2006;291:L802-10 pubmed
    ..These results indicate that the beta1-subunit is required in airway smooth muscle for control of voltage-dependent Ca2+ influx during rest and after cholinergic signaling in BK channels. ..
  29. Hagen B, Sanders K. Deglycosylation of the beta1-subunit of the BK channel changes its biophysical properties. Am J Physiol Cell Physiol. 2006;291:C750-6 pubmed
    ..These data suggest that glycosylations on the beta1-subunit in smooth muscle cells can modify the biophysical properties of BK channels. ..
  30. Figueroa X, Chen C, Campbell K, Damon D, Day K, Ramos S, et al. Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone?. Am J Physiol Heart Circ Physiol. 2007;293:H1371-83 pubmed
    ..2 channels. The resultant Ca(2+) influx activates endothelial nitric oxide synthase and Ca(2+)-activated K(+) channels, triggering vasodilation. ..
  31. Petkov G, Bonev A, Heppner T, Brenner R, Aldrich R, Nelson M. Beta1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle. J Physiol. 2001;537:443-52 pubmed
    ..8. The results indicate that the beta1-subunit, by modulating BK channel activity, plays a significant role in the regulation of phasic contractions of the urinary bladder. ..
  32. Li Y, Wang X, Sun X, Chai Q, Li J, Thompson B, et al. Regulation of vascular large-conductance calcium-activated potassium channels by Nrf2 signalling. Diab Vasc Dis Res. 2017;14:353-362 pubmed publisher
    ..Nrf2 should be considered a novel therapeutic target in the treatment of diabetic vasculopathy. ..
  33. Grimm P, Irsik D, Liu L, Holtzclaw J, Sansom S. Role of BKbeta1 in Na+ reabsorption by cortical collecting ducts of Na+-deprived mice. Am J Physiol Renal Physiol. 2009;297:F420-8 pubmed publisher
    ..Immunohistochemical staining revealed that BKalpha and BKbeta1, which were absent in the principal cells (PCs) of the CCD, were localized on the basolateral membrane (BSM) of ..
  34. Zheng Y, Park S, Stokes L, Tang Q, Xiao J, Wang Y. Distinct activity of BK channel β1-subunit in cerebral and pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol. 2013;304:C780-9 pubmed publisher
    ..This heterogeneity is primarily determined by the differential β(1)-subunit function and contributes to diverse cellular responses in these two distinct types of cells. ..
  35. Li M, Zhang Z, Koh H, Lu R, Jiang Z, Alioua A, et al. The ?1-subunit of the MaxiK channel associates with the thromboxane A2 receptor and reduces thromboxane A2 functional effects. J Biol Chem. 2013;288:3668-77 pubmed publisher
  36. Wang B, Rothberg B, Brenner R. Mechanism of beta4 subunit modulation of BK channels. J Gen Physiol. 2006;127:449-65 pubmed
    ..However, beta4 confers a compensatory effect on voltage sensor activation that increases channel opening during depolarization. ..
  37. Xu H, Garver H, Galligan J, Fink G. Large-conductance Ca2+-activated K+ channel beta1-subunit knockout mice are not hypertensive. Am J Physiol Heart Circ Physiol. 2011;300:H476-85 pubmed publisher
    ..BK and L-type Ca(2+) channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension. ..
  38. Wang X, Fisher P, Xi L, Kukreja R. Essential role of mitochondrial Ca2+-activated and ATP-sensitive K+ channels in sildenafil-induced late cardioprotection. J Mol Cell Cardiol. 2008;44:105-13 pubmed
    ..The results suggest that activation of mitoK(Ca) and mitoK(ATP) are crucial for maintaining mitochondrial homeostasis and reducing cell death in sildenafil-induced preconditioning against ischemia-reperfusion injury. ..