Вплив N-стеароїл- та N-олеоїлетаноламіну на потенціалзалежні натрієві канали кардіоміоцитів

Abstract

The group of N-acylethanolamines (NAE) includes lipids that are capable of modulating plasma membrane ion channels without involvement of cannabinoid receptors. However, the action of various members of NAE on voltage-gated Na+ channels (VGSC) in cardiac tissue is still not fully elucidated. Here using patch-clamp technique we have studied the modulation of biophysical properties of VGSC of neonatal cardiomyocytes by saturated N-stearoylethanolamine (NSE) and monounsaturated N-oleoylethanolamine (OEA). NSE in 1-200 tM concentration range did not significantly alter the amplitude of inward Na+ current (I(Na)), but 100 microM NSE shifted its steady-state activation and inactivation curves in hyperpolarization direction by 2.4 mV and 10.6 mV, respectively. Activation kinetics of the current was not changed by NSE, but its inactivation was accelerated by about 1.2-fold in the -60 - -30 mV range of membrane potentials. Unlike NSE, OEA dose-dependently inhibited I(Na) with kappa(D) = 11.4 +/- 1.6 microM and maximal block at saturating concentration of 30 +/- 3%. It also stronger than NSE shifted current's steady-state activation and inactivation curves (-6.4 mV and -14.0 mV, respectively, at 100 microM) in hyperpolarization direction. The effect of OEA on I(Na) activation kinetics was negligible, but it more pronouncedly than NSE accelerated inactivation of the current. Thus, both members of NAE influence the voltage-dependence of activation, inactivation and kinetics of I(Na). These effects were more prominent for monounsaturated OEA, which also partially blocked I(Na). The discovered effects of NSE and OEA on VGSCs may in part be responsible for the decrease of cardiomycytes' excitability by these lipids under normal as well as pathologic conditions.