Effects of N-stearoyl- and N-oleoylethanolamine on cardiac voltage-dependent sodium channels
Voĭtychuk OI, Asmolkova VS, Hula NM, Oz M, Shuba IaM
- International center for molecular physiology of the Nationalacademy of sciences of Ukraine, Kyiv, Ukraine
- Palladin Institute of biochemistry of the National academy ofsciences of Ukraine, Kyiv, Ukraine
- Department of Pharmacology, Faculty of Medicine andHealth Sciences, UAE University, Al Ain, UAE
DOI: https://doi.org/10.15407/fz56.05.013
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 cardio-myocytes by saturated N-stearoylethanolamine (NSE) and monounsaturated N-oleoylethanolamine (OEA). NSE in 1-200 HM concentration range did not significantly alter the amplitude of inward Na+ current (T ), but 100 uM NSE shifted its steady-state activation and inactivation curves in hyper-polarization 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 T with К = 11.4±1.6 uM 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 uM) in hyperpolarization direction. The effect of OEA on T 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 T . These effects were more prominent for monounsaturated OEA, which also partially blocked T . 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.
Keywords:
neonatal cardiomyocytes, N-acylethanolamines,voltage-dependent sodium channels, inactivation.
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