Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension

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• dc.contributor.author Fernández-Fernández, José Manuel, 1967-ca
• dc.contributor.author Tomás Mestres, Martaca
• dc.contributor.author Vázquez Gómez, Estherca
• dc.contributor.author Orio, Patricioca
• dc.contributor.author Latorre, Ramónca
• dc.contributor.author Sentí Clapés, Marianoca
• dc.contributor.author Marrugat de la Iglesia, Jaumeca
• dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-ca
• dc.date.accessioned 2016-01-21T17:47:48Z
• dc.date.available 2016-01-21T17:47:48Z
• dc.date.issued 2004
• dc.description.abstract Hypertension is the most prevalent risk factor for cardiovascular diseases, present in almost 30% of adults. A key element in the control of vascular tone is the large-conductance, Ca(2+)-dependent K(+) (BK) channel. The BK channel in vascular smooth muscle is formed by an ion-conducting alpha subunit and a regulatory beta(1) subunit, which couples local increases in intracellular Ca(2+) to augmented channel activity and vascular relaxation. 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. This mutation results in a gain of function of the channel and is associated with low prevalence of moderate and severe diastolic hypertension. BK-beta(1E65K) channels showed increased Ca(2+) sensitivity, compared with wild-type channels, without changes in channel kinetics. In conclusion, the BK-beta(1E65K) channel might offer a more efficient negative-feedback effect on vascular smooth muscle contractility, consistent with a protective effect of the K allele against the severity of diastolic hypertension.ca
• dc.description.sponsorship This work was supported by the Human Frontiers Science Organization, the Ministerio de Ciencia y Tecnología (Spain), Red HERACLES (Fondo de Investigaciones Sanitarias, Spain), Comissió Interdepartamental de Recerca i Innovació Tecnològica, de la Generalitat de Catalunya per a la Promoció de la Recerca Universitaria, and Fondo Nacional de Investigaciones Científicas y Tecnológicas (Chile)
• dc.format.mimetype application/pdfca
• dc.identifier.citation Fernández-Fernández JM, Tomás M, Vázquez E, Orio P, Latorre R, Sentí M et al. Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension. Journal of clinical investigation. 2004;113(7):1032-9. DOI: 10.1172/JCI20347ca
• dc.identifier.doi http://dx.doi.org/10.1172/JCI20347
• dc.identifier.issn 0021-9738
• dc.identifier.uri http://hdl.handle.net/10230/25630
• dc.language.iso engca
• dc.publisher American Society for Clinical Investigationca
• dc.relation.ispartof Journal of clinical investigation. 2004;113(7):1032-9
• dc.rights © American Society for Clinical Investigationca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Hipertensióca
• dc.subject.other Canals de potassica
• dc.title Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertensionca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca