Título:
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Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension
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Autor/a:
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Fernández-Fernández, José Manuel, 1967-; Tomás Mestres, Marta; Vázquez Gómez, Esther; Orio, Patricio; Latorre, Ramón; Sentí Clapés, Mariano; Marrugat de la Iglesia, Jaume; Valverde, M. A. (Miguel Ángel), 1963-
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Abstract:
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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. |
Abstract:
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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) |
Materia(s):
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-Hipertensió -Canals de potassi |
Derechos:
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© American Society for Clinical Investigation
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Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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American Society for Clinical Investigation
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