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Gene Review

KCNMB1  -  potassium channel subfamily M regulatory...

Homo sapiens

Synonyms: BK channel subunit beta-1, BKbeta, BKbeta1, Calcium-activated potassium channel subunit beta, Calcium-activated potassium channel subunit beta-1, ...
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Disease relevance of KCNMB1


High impact information on KCNMB1

  • The BK beta1-subunit, which is expressed in smooth muscle, increases the apparent Ca(2+) sensitivity (marked by a hyperpolarizing shift in the conductance-voltage relationship at a given Ca(2+) concentration), slows macroscopic activation and deactivation, and is required for channel activation by 17beta-estradiol [5].
  • 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 [3].
  • The coexpression of hslo-beta mRNA together with hslo-alpha subunits in either Xenopus oocytes or stably transfected HEK 293 cells give rise to Ca(2+)-activated potassium currents with a much increased calcium and/or voltage sensitivity [6].
  • The gene for this subunit is located on chromosome 5 at band q34 (hslo-beta) [6].
  • DNA from three cell lines, digested with several restriction enzymes, produced a pattern providing evidence for the presence of circular H beta 1 molecules in the murine recipient cells [7].

Biological context of KCNMB1


Anatomical context of KCNMB1

  • Consistent with a tissue-specific expression of KCNMB1, regulated at the transcriptional level, beta-subunit transcripts are abundant in smooth muscle and heart, but scarce in lymphatic tissues, brain, and liver [11].
  • Our studies revealed that BKbeta1 interacts with cytochrome c oxidase I (Cco1) in cardiac mitochondria, and that the activation of BK channels by 17beta-estradiol results in a significant increase in the survival rate of ventricular myocytes [12].
  • These findings suggest that BKbeta1 may play an important role in the regulation of cell respiration in cardiac myocytes and be a target for the modulation by female gonadal hormones [12].
  • Expression of BK beta1 in mesenteric arteries is closely correlated with BP in SHR [13].
  • 5. In the prostatic vas deferens, halpha-CGRP, hbeta-CGRP and rat beta-CGRP (10(-10) - 3 x 10(-7) M) concentration-dependently inhibited twitch responses with about equal potency, while rat amylin (10(-8) - 10(-5) M) was around 10 fold less potent and the linear analogue [Cys(ACM2,7)] halpha-CGRP was at least 3000 fold weaker [14].

Associations of KCNMB1 with chemical compounds

  • Internal dialysis of human embryonic kidney cells stably expressing CLCA1 with 500 nM Ca(2+) evoked a significantly larger current when the beta-subunit KCNMB1 was co-expressed [15].
  • Thus our results argue that the variety of Slo-beta subunit coexpression patterns occurring in vivo expands the repertoire of Slo channel gating in yet another dimension not fully appreciated, rendering BK gating responsive to dynamic fluctuations in a multiple of steroid hormones [16].
  • CONCLUSIONS: The deletion of BKbeta1 causes endothelial dysfunction by increasing O2- formation via increasing activity and expression of the vascular NADPH oxidase [17].
  • By targeting a cysteine residue near the Ca(2+) bowl of the BK alpha subunit, H(2)O(2) virtually eliminates physiological activation of the channel, with an inhibitory potency comparable to a knockout of the auxiliary subunit BK beta 1 [18].
  • There is one Cys residue in the single TM segment of beta-subunit (Hbeta) [19].

Other interactions of KCNMB1

  • BKbeta4 slowed activation kinetics more significantly, led to a steeper apparent calcium sensitivity, and shifted the voltage range of BK current activation to more negative potentials than BKbeta1 [20].
  • Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population--the Suita Study [21].
  • The significance of the CLCNKB/T481S and KCNMB1/E65K polymorphisms were not replicated in the present study [21].
  • Other proton interactions were tentatively assigned to H beta 1 of His-44, H delta 2 of His-46 and to H beta 2 of His-44 [22].
  • 4 Human alpha-CGRP8-37 (3 x 10(-7) - 3 x 10(-6) M) antagonized halpha-CGRP (pA2 6.9, Schild plot slope 1.2+/-0.1) and hbeta-CGRP (apparent pKB of 7.1+/-0.1 for halpha-CGRP8-37 10(-6) M) in the pulmonary artery [14].

Analytical, diagnostic and therapeutic context of KCNMB1

  • Our large population-based genetic epidemiological study has identified a new single-nucleotide substitution (G352A) in the beta(1) gene (KCNMB1), corresponding to an E65K mutation in the protein [1].
  • Both *OOH and O2*- adducts, with different 14N and Hbeta splittings, were detected simultaneously in some samples, for the first time in the spin trapping literature [23].


  1. Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension. Fernández-Fernández, J.M., Tomás, M., Vázquez, E., Orio, P., Latorre, R., Sentí, M., Marrugat, J., Valverde, M.A. J. Clin. Invest. (2004) [Pubmed]
  2. E65 K polymorphism in KCNMB1 gene is not associated with ischaemic heart disease in Spanish patients. Via, M., Valveny, N., López-Alomar, A., Athanasiadis, G., Pintó, X., Domingo, E., Esteban, E., González-Pérez, E., Moral, P. J. Hum. Genet. (2005) [Pubmed]
  3. Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BKbeta1-subunit leads to progressive hearing loss. Rüttiger, L., Sausbier, M., Zimmermann, U., Winter, H., Braig, C., Engel, J., Knirsch, M., Arntz, C., Langer, P., Hirt, B., Müller, M., Köpschall, I., Pfister, M., Münkner, S., Rohbock, K., Pfaff, I., Rüsch, A., Ruth, P., Knipper, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Cord blood transplantation (CBT) in hemoglobinopathies. Eurocord. Miniero, R., Rocha, V., Saracco, P., Locatelli, F., Brichard, B., Nagler, A., Roberts, I., Yaniv, I., Beksac, M., Bernaudin, F., Gluckman, E. Bone Marrow Transplant. (1998) [Pubmed]
  5. Defining the BK channel domains required for beta1-subunit modulation. Morrow, J.P., Zakharov, S.I., Liu, G., Yang, L., Sok, A.J., Marx, S.O. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Cloning, expression, and distribution of a Ca(2+)-activated K+ channel beta-subunit from human brain. Tseng-Crank, J., Godinot, N., Johansen, T.E., Ahring, P.K., Strøbaek, D., Mertz, R., Foster, C.D., Olesen, S.P., Reinhart, P.H. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. DNA-mediated gene transfer of a circular plasmid into murine cells. Huttner, K.M., Scangos, G.A., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  8. The BK channel beta1 subunit gene is associated with human baroreflex and blood pressure regulation. Gollasch, M., Tank, J., Luft, F.C., Jordan, J., Maass, P., Krasko, C., Sharma, A.M., Busjahn, A., Bähring, S. J. Hypertens. (2002) [Pubmed]
  9. Protective effect of the KCNMB1 E65K genetic polymorphism against diastolic hypertension in aging women and its relevance to cardiovascular risk. Sentí, M., Fernández-Fernández, J.M., Tomás, M., Vázquez, E., Elosua, R., Marrugat, J., Valverde, M.A. Circ. Res. (2005) [Pubmed]
  10. Phenotypic alteration of a human BK (hSlo) channel by hSlobeta subunit coexpression: changes in blocker sensitivity, activation/relaxation and inactivation kinetics, and protein kinase A modulation. Dworetzky, S.I., Boissard, C.G., Lum-Ragan, J.T., McKay, M.C., Post-Munson, D.J., Trojnacki, J.T., Chang, C.P., Gribkoff, V.K. J. Neurosci. (1996) [Pubmed]
  11. Human and rodent MaxiK channel beta-subunit genes: cloning and characterization. Jiang, Z., Wallner, M., Meera, P., Toro, L. Genomics (1999) [Pubmed]
  12. Molecular pharmacological studies on potassium channels and their regulatory molecules. Ohya, S. Yakugaku Zasshi (2006) [Pubmed]
  13. Altered expression of BK channel beta1 subunit in vascular tissues from spontaneously hypertensive rats. Chang, T., Wu, L., Wang, R. Am. J. Hypertens. (2006) [Pubmed]
  14. Pharmacological characterization of CGRP receptors mediating relaxation of the rat pulmonary artery and inhibition of twitch responses of the rat vas deferens. Wisskirchen, F.M., Burt, R.P., Marshall, I. Br. J. Pharmacol. (1998) [Pubmed]
  15. The large conductance potassium channel beta-subunit can interact with and modulate the functional properties of a calcium-activated chloride channel, CLCA1. Greenwood, I.A., Miller, L.J., Ohya, S., Horowitz, B. J. Biol. Chem. (2002) [Pubmed]
  16. Beta2 and beta4 subunits of BK channels confer differential sensitivity to acute modulation by steroid hormones. King, J.T., Lovell, P.V., Rishniw, M., Kotlikoff, M.I., Zeeman, M.L., McCobb, D.P. J. Neurophysiol. (2006) [Pubmed]
  17. NADPH oxidase accounts for enhanced superoxide production and impaired endothelium-dependent smooth muscle relaxation in BKbeta1-/- mice. Oelze, M., Warnholtz, A., Faulhaber, J., Wenzel, P., Kleschyov, A.L., Coldewey, M., Hink, U., Pongs, O., Fleming, I., Wassmann, S., Meinertz, T., Ehmke, H., Daiber, A., Münzel, T. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  18. Reactive oxygen species impair Slo1 BK channel function by altering cysteine-mediated calcium sensing. Tang, X.D., Garcia, M.L., Heinemann, S.H., Hoshi, T. Nat. Struct. Mol. Biol. (2004) [Pubmed]
  19. Packing of the transmembrane helices of Na,K-ATPase: direct contact between beta-subunit and H8 segment of alpha-subunit revealed by oxidative cross-linking. Ivanov, A., Zhao, H., Modyanov, N.N. Biochemistry (2000) [Pubmed]
  20. hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family. Behrens, R., Nolting, A., Reimann, F., Schwarz, M., Waldschütz, R., Pongs, O. FEBS Lett. (2000) [Pubmed]
  21. Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population--the Suita Study. Kokubo, Y., Iwai, N., Tago, N., Inamoto, N., Okayama, A., Yamawaki, H., Naraba, H., Tomoike, H. Circ. J. (2005) [Pubmed]
  22. An ENDOR study of human and bovine erythrocyte superoxide dismutase: 1H and 14N interactions. Hüttermann, J., Kappl, R., Banci, L., Bertini, I. Biochim. Biophys. Acta (1988) [Pubmed]
  23. Spin trapping by 5,5-dimethylpyrroline-N-oxide in Fenton media in the presence of Nafion perfluorinated membranes: limitations and potential. Bosnjakovic, A., Schlick, S. The journal of physical chemistry. B, Condensed matter, materials, surfaces, interfaces & biophysical. (2006) [Pubmed]
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