REGULATION OF THE EXCITABILITY OF NEONATAL CARDIOMYOCYTES BY N-STEARYL- AND N-OLEYLETHANOLAMINES
O.I. Voitychuk1, V.S. Asmolkova2, N.M. Gula2, G.V. Sotkis1, M. Oz3, Y.M. Shuba1
- International Center of Molecular Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
- Palladin Institute of Biochemistry of the National Academy of
Sciences of Ukraine, Kyiv, Ukraine
- Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, UAE
N-acylethanolamines (NAE) are biologically active lipids able of modulating ion transport through the cellular plasma membrane, however specific targets of their action and signalling mechanisms involved in cardiac tissue are still poorly understood. Physiological activity of NAEs is known to depend on the level of unsaturation. Therefore, here we investigated the effects of saturated N-stearylethanolamine (NSE) and monounsaturated N-oleylethanolamine on electric excitability of neonatal rat cardiomyocytes. 1 HM of either NSE or OEA decreased the duration of cardiac action potential (AP) from all parts of heart muscle. Shortening of AP was partially reversible, though the reversibility of AP duration upon washout of substances was more complete for endocardial ventricular compared to epicardial and atrial cardiomyocytes. 1 ^M NSE depolarized resting membrane potential (RMP) of epicardial and of 65% of endocardial cells, whilst other cells types showed weakly reversible hyperpolarization. 1 HM OEA caused reversible RMP hyperpolarization of all studied cell types. NSE and OEA decreased the amplitude and upstroke velocity of AP that suggests their effect on sodium channels. NSE and to a lesser extent OEA inhibited the amplitude of AP phase 2 (plateau) which may indicate an inhibition of high-voltage-activated calcium channels. Effects of NSE and OEA on RMP and repolarization phase of AP (phase 3) depended on cardiac cell type suggesting differential regulation of inward rectifier Kir and voltage-gated delayed rectifier potassium channels by these lipids. We cannot also exclude interaction of NSE and OEA with anion channels, backgound K+ channels and ion transporters of the cardiomyocytes’ plasma membrane. Overall, NSE-induced changes of AP parameters were less reversible than those induced by OEA, suggesting a slower degradation/ convertion of NSE in plasma membrane compared to OEA.
N-acylethanolamines, N-stearylethanolamine, cardiomyocytes, rat
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