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

Fernandez-Fernandez, JM; Tomàs M.; Vazquez, E; Orio, P; Latorre R.; Senti, M; Marrugat, J; Valverde, MA

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, Ca2+-dependent K+ (BK) channel. The BK channel in vascular smooth muscle is formed by an ion-conducting ? subunit and a regulatory ?1 subunit, which couples local increases in intracellular Ca2+ to augmented channel activity and vascular relaxation. Our large population-based genetic epidemiological study has identified a new single-nucleotide substitution (G352A) in the ? 1 gene (KCNMB1), corresponding to an E6SK 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-?1E65K channels showed increased Ca2+ sensitivity, compared with wild-type channels, without changes in channel kinetics. In conclusion, the BK-?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.

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Título según WOS: Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension
Título según SCOPUS: Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension
Título de la Revista: JOURNAL OF CLINICAL INVESTIGATION
Volumen: 113
Número: 7
Editorial: AMER SOC CLINICAL INVESTIGATION INC
Fecha de publicación: 2004
Página de inicio: 1032
Página final: 1039
Idioma: English
DOI:

10.1172/JCI200420347

Notas: ISI, SCOPUS