Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension
作者： José M Fernández-Fernández , Marta Tomás , Esther Vázquez , Patricio Orio , Ramón Latorre
DOI: 10.1172/JCI20347
关键词: Contractility 、 Beta (finance) 、 Patch clamp 、 Chemistry 、 Potassium channel 、 BK channel 、 G alpha subunit 、 Diastolic Hypertension 、 Endocrinology 、 Internal medicine 、 Vascular smooth muscle
摘要: Hypertension is the most prevalent risk factor for cardiovascular diseases, present in almost 30% of adults. A key element control vascular tone large-conductance, Ca(2+)-dependent K(+) (BK) channel. The BK channel smooth muscle formed by an ion-conducting alpha subunit and a regulatory beta(1) subunit, which couples local increases intracellular Ca(2+) to augmented activity relaxation. Our large population-based genetic epidemiological study has identified new single-nucleotide substitution (G352A) gene (KCNMB1), corresponding E65K mutation protein. This results gain function associated with low prevalence moderate severe diastolic hypertension. BK-beta(1E65K) channels showed increased sensitivity, compared wild-type channels, without changes kinetics. In conclusion, might offer more efficient negative-feedback effect on contractility, consistent protective K allele against severity
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