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 2+ channels; and epithelial Na + channels. The present study was aimed to check the RhoA potential regulatory effects on Na + current (I Na ) transferred by Na + channel cardiac isoform Na V 1.5 in heterologous expression system and in native rat cardiomyocytes. Whole-cell patch-clamp experiments showed that coexpression of Na V 1.5 with the wild-type RhoA in CHO-K1 cell line caused 2.7-fold decrease of I Na 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 −6 M) reduced the maximal I Na density by 38.8%. The RhoA-selective inhibitor rhosin (10 −5 M) increased the maximal I Na density by 25.3%. Experiments with sharp microelectrode recordings in isolated right ventricular wall preparations showed that 5 × 10 −6 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 Na V 1.5.