Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension
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.
|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|
|Editorial:||AMER SOC CLINICAL INVESTIGATION INC|
|Fecha de publicación:||2004|
|Página de inicio:||1032|