Regulation of Na V 1.5 Sodium Channels by Small G-Proteins of the Rho Family in a Heterologous Expression System
- PDF / 528,858 Bytes
- 5 Pages / 594 x 792 pts Page_size
- 21 Downloads / 192 Views
Bulletin of Experimental Biology and Medicine, Vol. 169, No. 6, October, 2020 PHYSIOLOGY
729
Regulation of NaV1.5 Sodium Channels by Small G-Proteins of the Rho Family in a Heterologous Expression System D. V. Abramochkin1,2, K. B. Pustovit1,2, A. S. Bilichenko2, A. Yu. Khushkina3, and A. V. Karpushev3
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 6, pp. 668-672, June, 2020 Original article submitted February 26, 2020 The effect of small G-proteins of the Rho family on sodium current conducted by cardiac isoform NaV1.5 of voltage-gated sodium channels was studied in heterologous expression system, CHO-K1 cell line transfected with a plasmid containing the NaV1.5 gene. The influence of cotransfection with genes of wild-type, constitutively-active, and dominant-negative small G-proteins RhoA, Rac1, and Cdc2 on the parameters of sodium current and its noninactivating component (INa,late) was estimated. Among three studied small G-proteins, only RhoA (wild-type and constitutively-active type) strongly affected sodium current reducing its peak amplitude, but not the value of INa,late. Cotransfection with wild-type Rac1 resulted in a minor decrease in sodium current. Thus, small G-protein RhoA has potential capability for suppression of sodium current, although physiological relevance of this property has to be verified. Key Words: sodium channels; ionic currents; patch-clamp; myocardium; small G-proteins NaV1.5, the so-called cardiac isoform of voltage-gated sodium channels, is crucially important for myocardial function, because it is responsible for depolarization phase of the action potential in working atrial and ventricular cardiomyocytes and in the fibers of cardiac conduction system. The magnitude of fast sodium current INa conducted by NaV1.5 determines action potential upstroke velocity and thereby, excitation conduction velocity in the myocardial tissue. Various mutations in the SCN5A gene encoding pore-forming α-subunit of NaV1.5 were described. Some of them are associated with severe inherited diseases, such as Brugada syndrome, long QT syndrome type 3 (LQT3), idiopathic ventricular fibrillation, and various pathologies of the cardiac conduction system [2,4,10]. Cardiac sodium channels represent an important target for antiarrhythDepartment of Human and Animal Physiology, M. V. Lomonosov Moscow State University, Moscow, Russia; 2Research Laboratory of Electrophysiology, N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia; 3V. A. Almazov National Medical Research Center, Ministry of Health of the Russian Federation, St. Petersburg, Russia. Address for correspondence: [email protected]. D. V. Abramochkin 1
mic drugs. Compounds affecting the non-inactivating component of sodium current, the so-called late current INa,late, are of special interest due to important pathophysiological role of INa,late [5,8]. In light of this, the search for new ways of modulation of sodium current and particularly, of its non
Data Loading...
