Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2010; 56(5): 13-22

Effects of N-stearoyl- and N-oleoylethanolamine on cardiac voltage-dependent sodium channels

Voĭtychuk OI, Asmolkova VS, Hula NM, Oz M, Shuba IaM

  1. International center for molecular physiology of the Nationalacademy of sciences of Ukraine, Kyiv, Ukraine
  2. Palladin Institute of biochemistry of the National academy ofsciences of Ukraine, Kyiv, Ukraine
  3. 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.

Keywords: neonatal cardiomyocytes, N-acylethanolamines,voltage-dependent sodium channels, inactivation.


  1. Alexander S.P., Kendall D.A. The complications of promiscuity: endocannabinoid action and metabolism . Brit. J. Pharmacol. 2007. 152, N 5. P. 602-623. CrossRef PubMed PubMedCentral
  3. Bachur N.R., Masek K., Melmon K.L., Udenfriend S. Fatty Acid Amides of Ethanolamine in Mammalian Tissues . J. Biol. Chem. 1965. 240, N 3. P. 1019-1024.
  5. Bradshaw H.B., Walker J.M. The expanding field of cannabimimetic and related lipid mediators . Brit. J. Pharmacol. 2005. 144, N 4. P. 459-465. CrossRef PubMed PubMedCentral
  7. 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, N 24. P. 7033-7040. CrossRef PubMed PubMedCentral
  9. Chemin J., Nargeot J., Lory P. Chemical determinants involved in anandamide-induced inhibition of T-type calcium channels . J. Biol. Chem. 2007. 282, N 4. P. 2314-2323. CrossRef PubMed
  11. Chen C, Bazan N.G. Lipid signaling: sleep, synaptic plasticity, and neuroprotection . Prostaglandins and Other Lipid Mediat. 2005. 77, N 1-4. P. 65-76. CrossRef PubMed
  13. Di Marzo V., Melck D., De Petrocellis L., Bisogno T. Cannabimimetic fatty acid derivatives in cancer and inflammation . Ibid. 2000. 61, N 1-2. P. 43-61. CrossRef  
  14. Freund T.F., Katona I., Piomelli D. Role of endog­enous cannabinoids in synaptic signaling . Physiol Rev. 2003. 83, N 3. P. 1017-1066. CrossRef PubMed
  16. 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, N 1. P. 56-63.
  18. 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, N 1. P. 85-91. CrossRef PubMed
  20. 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, N 2. P. 280-288. CrossRef  
  21. Hiley C.R., Hoi P.M. Oleamide: a fatty acid amide signaling molecule in the cardiovascular system? . Cardiovasc Drug Rev. 2007. 25, N 1. P. 46-60. CrossRef PubMed
  23. 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, N 1-2. P. 39-47. CrossRef PubMed
  25. 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, N 3. P. 355-377. CrossRef  
  26. 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, N 1-2. P. 194-204. CrossRef  
  27. Oz M. Receptor-independent effects of endoca-nnabinoids on ion channels . Curr Pharm. and Des. 2006. 12, N 2. P. 227-239. CrossRef PubMed
  29. Park K.A., Vasko M.R. Lipid mediators of sensitivity in sensory neurons . Trends Pharmacol Sci. 2005. 26, N 11. P. 571-577. CrossRef PubMed
  31. 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, N 2. P. 438-444.
  33. 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, N 1-2. P. 111-134. CrossRef  
  34. Schuel H., Burkman L.J. A tale of two cells: endocannabinoid-signaling regulates functions ofneurons and sperm . Biol. Reprod. 2005. 73, N 6. P. 1078-1086.
  36. 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, N 10. P. 4127-4133. CrossRef PubMed PubMedCentral
  38. 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, N 3. P. 55-66.
  40. Wang J., Ueda N. Biology of endocannabinoid synthe­sis system . Prostaglandins Other Lipid Mediat. 2009. 89, N 3-4. P. 112-119. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.