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

Autor: Tatiana S. Filatova, Denis V. Abramochkin, Alexey V. Karpushev, K. B. Pustovit, Irina Dzhumaniiazova
Rok vydání: 2020
Předmět:
Zdroj: Journal of Physiology and Biochemistry. 77:13-23
ISSN: 1877-8755
1138-7548
Popis: Small G-proteins of Rho family modulate the activity of several classes of ion channels, including K+ channels Kv1.2, Kir2.1, and ERG; Ca2+ channels; and epithelial Na+ channels. The present study was aimed to check the RhoA potential regulatory effects on Na+ current (INa) transferred by Na+ channel cardiac isoform NaV1.5 in heterologous expression system and in native rat cardiomyocytes. Whole-cell patch-clamp experiments showed that coexpression of NaV1.5 with the wild-type RhoA in CHO-K1 cell line caused 2.7-fold decrease of INa 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 INa density by 38.8%. The RhoA-selective inhibitor rhosin (10−5 M) increased the maximal INa 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 NaV1.5.
Databáze: OpenAIRE
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