Small G-protein RhoA is a potential inhibitor of cardiac fast sodium current.

Small G-proteins of Rho family modulate the activity of several classes of ion channels, including K channels Kv1.2, Kir2.1, and ERG; Ca channels; and epithelial Na channels. The present study was aimed to check the RhoA potential regulatory effects on Na current (I) transferred by Na channel cardiac isoform Na1.5 in heterologous expression system and in native rat cardiomyocytes. Whole-cell patch-clamp experiments showed that coexpression of Na1.5 with the wild-type RhoA in CHO-K1 cell line caused 2.7-fold decrease of I density with minimal influence on steady-state activation and inactivation. This effect was reproduced by the coexpression with a constitutively active RhoA, but not with a dominant negative RhoA. In isolated ventricular rat cardiomyocytes, a 5-h incubation with the RhoA activator narciclasine (5 × 10 M) reduced the maximal I density by 38.8%. The RhoA-selective inhibitor rhosin (10 M) increased the maximal I density by 25.3%. Experiments with sharp microelectrode recordings in isolated right ventricular wall preparations showed that 5 × 10 M narciclasine induced a significant reduction of action potential upstroke velocity after 2 h of incubation. Thus, RhoA might be considered as a potential negative regulator of sodium channels cardiac isoform Na1.5.