title: Modulation of excitability, membrane currents and survival of cardiac myocytes by N-acylethanolamines.
abstract: N-acylethanolamines (NAE) are endogenously produced lipids playing important roles in a diverse range of physiological and pathological conditions. In the present study, using whole-cell patch clamp technique, we have for the first time investigated the effects of the most abundantly produced NAEs, N-stearoylethanolamine (SEA) and N-oleoylethanolamine (OEA), on electric excitability and membrane currents in cardiomyocytes isolated from endocardial, epicardial, and atrial regions of neonatal rat heart. SEA and OEA (1-10μM) attenuated electrical activity of the myocytes from all regions of the cardiac muscle by hyperpolarizing resting potential, reducing amplitude, and shortening the duration of the action potential. However, the magnitudes of these effects varied significantly depending on the type of cardiac myocyte (i.e., endocardial, epicardial, atrial) with OEA being generally more potent. OEA and to a lesser extent SEA suppressed in a concentration-dependent manner currents through voltage-gated Na(+) (VGSC) and L-type Ca(2+) (VGCC) channels, but induced variable cardiac myocyte type-dependent effects on background K(+) and Cl(-) conductance. The mechanisms of inhibitory action of OEA on cardiac VGSCs and VGCCs involved influence on channels' activation/inactivation gating and partial blockade of ion permeation. OEA also enhanced the viability of cardiac myocytes by reducing necrosis without a significant effect on apoptosis. We conclude that SEA and OEA attenuate the excitability of cardiac myocytes mainly through inhibition of VGSCs and VGCC-mediated Ca(2+) entry. Since NAEs are known to increase during tissue ischemia and infarction, these effects of NAEs may mediate some of their cardioprotective actions during these pathological conditions.
authors.affiliation: International Center of Molecular Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Oleg I
authors.initials: OI
authors.lastname: Voitychuk
authors.forename: Valentyna S
authors.initials: VS
authors.lastname: Asmolkova
authors.forename: Nadiya M
authors.initials: NM
authors.lastname: Gula
authors.forename: Ganna V
authors.initials: GV
authors.lastname: Sotkis
authors.forename: Sehamuddin
authors.initials: S
authors.lastname: Galadari
authors.forename: Frank C
authors.initials: FC
authors.lastname: Howarth
authors.forename: Murat
authors.initials: M
authors.lastname: Oz
authors.forename: Yaroslav M
authors.initials: YM
authors.lastname: Shuba
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D063388:Endocannabinoids / Q000378:metabolism / Q000494:pharmacology*; D004983:Ethanolamines / Q000378:metabolism / Q000494:pharmacology*; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009829:Oleic Acids / Q000378:metabolism / Q000494:pharmacology*; D010496:Pericardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013229:Stearic Acids / Q000378:metabolism / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D063388:Endocannabinoids; D004983:Ethanolamines; C408368:N-stearoylethanolamine; D009829:Oleic Acids; D013229:Stearic Acids; D061566:Voltage-Gated Sodium Channels; C033595:N-oleoylethanolamine