The effects of n-stearoyl- andn-oleoylethanolamine on cardiacvoltage-dependent sodium channels
O.I. Voitychuk, V.S. Asmolkova, N.M. Gula,M.Oz, Y.M. Shuba.
International center for molecular physiology of the Nationalacademy of sciences of Ukraine, Kyiv;Palladin Institute of biochemistry of the National academy ofsciences of Ukraine, Kyiv;Department of Pharmacology, Faculty of Medicine andHealth Sciences, UAE University, Al Ain, UAE
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.
neonatal cardiomyocytes, N-acylethanolamines,voltage-dependent sodium channels, inactivation.
- Alexander S.P., Kendall D.A. The complications of promiscuity: endocannabinoid action and metabolism // Brit. J. Pharmacol. - 2007. - 152, № 5. - P. 602-623.
- Bachur N.R., Masek K., Melmon K.L., Udenfriend S. Fatty Acid Amides of Ethanolamine in Mammalian Tissues // J. Biol. Chem. - 1965. - 240, № 3. -P. 1019-1024.
- Bradshaw H.B., Walker J.M. The expanding field of cannabimimetic and related lipid mediators // Brit. J. Pharmacol. - 2005. - 144, № 4. - P. 459-465.
- Chemin J., Monteil A., Perez-Reyes E., Nargeot J., Lory P. Direct inhibition of T-type calcium channels by the endogenous cannabinoid anandamide // EMBO J. - 2001. - 20, № 24. - P. 7033-7040.
- Chemin J., Nargeot J., Lory P. Chemical determinants involved in anandamide-induced inhibition of T-type calcium channels // J. Biol. Chem. - 2007. - 282, № 4. -P. 2314-2323.
- Chen C, Bazan N.G. Lipid signaling: sleep, synaptic plasticity, and neuroprotection // Prostaglandins and Other Lipid Mediat. - 2005. - 77, № 1-4. - P. 65-76.
- Di Marzo V., Melck D., De Petrocellis L., Bisogno T. Cannabimimetic fatty acid derivatives in cancer and inflammation // Ibid. - 2000. - 61, № 1-2. - P. 43-61.
- Freund T.F., Katona I., Piomelli D. Role of endogenous cannabinoids in synaptic signaling // Physiol Rev. - 2003. - 83, №3. - P. 1017-1066.
- 9. Frol’kis V.V., Artamonov M.V., Zhukov O.D., Klimashevs’kii V.M., Marhitych V.M., Hula N.M. [Influence of saturated long-chain N-acylethanolamines on lipid composition and heart contractility of isolated rat heart under ischemia-reperfusion] // Ukr Biokhim Zh. - 2000. - 72, № 1. - P. 56-63.
- 10. Fu H., Xiao J.M., Cao X.H., Ming Z.Y., Liu L.J. Effects of WIN55,212-2 on voltage-gated sodium channels in trigeminal ganglion neurons of rats // Neurol Res. -2008. - 30, №1. - P. 85-91.
- Gulaya N.M., Melnik A.A., Balkov D.I., Volkov G.L., Vysotskiy M.V., Vaskovsky V.E. The effect of long-chain N-acylethanolamines on some membrane-associated functions of neuroblastoma C1300 N18 cells // Biochim. and Biophys. Acta. - 1993. - 1152, № 2. -P. 280-288.
- Hiley C.R., Hoi P.M. Oleamide: a fatty acid amide signaling molecule in the cardiovascular system? // Cardiovasc Drug Rev. - 2007. - 25, № 1. - P. 46-60.
- Kim H.I., Kim T.H., Shin Y.K., Lee C.S., Park M., Song J.H. Anandamide suppression of Na+ currents in rat dorsal root ganglion neurons // Brain Res. - 2005. -1062, № 1-2. - P. 39-47.
- Leaf A., Xiao Y.F., Kang J.X., Billman G.E. Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids // Pharmacol. Therap. - 2003. - 98, № 3. -P. 355-377.
- Nicholson R.A., Liao C, Zheng J., David L.S., Coyne L., Errington A.C., Singh G., Lees G. Sodium channel inhibition by anandamide and synthetic cannabi-mimetics in brain // Brain Res. - 2003. - 978, № 1-2. -P. 194-204.
- Oz M. Receptor-independent effects of endoca-nnabinoids on ion channels // Curr Pharm. and Des. -2006. - 12, № 2. - P. 227-239.
- Park K.A., Vasko M.R. Lipid mediators of sensitivity in sensory neurons // Trends Pharmacol Sci. - 2005. -26, №11. - P. 571-577.
- Rogers T.B., Gaa S.T., Allen I.S. Identification and characterization of functional angiotensin II receptors on cultured heart myocytes // J. Pharmacol. Exp. Therap. - 1986. - 236, № 2. - P. 438-444.
- 19. Schmid H.H., Schmid P.C., Berdyshev E.V. Cell signaling by endocannabinoids and their congeners: questions of selectivity and other challenges // Chem. Phys. Lipids. - 2002. - 121, № 1-2. - P. 111-134.
- 20. Schuel H., Burkman L.J. A tale of two cells: endocannabinoid-signaling regulates functions ofneurons and sperm // Biol. Reprod. - 2005. - 73, № 6. -P. 1078-1086. 21. Veldhuis W.B., van der Stelt M., Wadman M.W., van Zadelhoff G., Maccarrone M., Fezza F., Veldink G.A., Vliegenthart J.F., Bar P.R., Nicolay K., Di Marzo V. Neuroprotection by the endogenous cannabinoid anandamide and arvanil against in vivo excitotoxicity in the rat: role of vanilloid receptors and lipoxygenases // J. Neurosci. - 2003. - 23, № 10. - P. 4127-4133.
- Voitychuk O.I., Asmolkova VS., Hula N.M., Sotkis H.V., Oz M., Shuba Ia M. Regulation of the excitability of neonatal cardiomyocytes by N-stearoyl- and N-oleoyl-ethanolamines // Fiziol. Zh. - 2009. - 55, № 3. - P. 55-66.
- Wang J., Ueda N. Biology of endocannabinoid synthesis system // Prostaglandins Other Lipid Mediat. -2009. - 89, №3-4. - P. 112-119.