Small G-protein RhoA is a potential inhibitor of cardiac fast sodium currentстатья
Статья опубликована в высокорейтинговом журнале
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 21 июля 2021 г.
Аннотация:Small G-proteins of Rho family modulate the activity of several classes ofion channels, including K channels Kv1.2, Kir2.1, and ERG; Cachannels; and epithelial Na channels. The present study was aimed tocheck the RhoA potential regulatory effects on Na current (I ) transferredby Na channel cardiac isoform Na 1.5 in heterologous expression systemand in native rat cardiomyocytes. Whole-cell patch-clamp experimentsshowed that coexpression of Na 1.5 with the wild-type RhoA in CHO-K1cell line caused 2.7-fold decrease of I density with minimal influence onsteady-state activation and inactivation. This effect was reproduced by thecoexpression with a constitutively active RhoA, but not with a dominantnegative RhoA. In isolated ventricular rat cardiomyocytes, a 5-h incubationwith the RhoA activator narciclasine (5 × 10 M) reduced the maximal Idensity by 38.8%. The RhoA-selective inhibitor rhosin (10 M) increasedthe maximal I density by 25.3%. Experiments with sharp microelectroderecordings in isolated right ventricular wall preparations showed that 5 ×10 M narciclasine induced a significant reduction of action potentialupstroke velocity after 2 h of incubation. Thus, RhoA might be consideredas a potential negative regulator of sodium channels cardiac isoformNa 1.5.