Effects of endogenous cannabinoid anandamide on excitation-contraction coupling in rat ventricular myocytes

Lina T. Al Kury, Oleg I. Voitychuk, Ramiz M. Ali, Sehamuddin Galadari, Keun Hang Susan Yang, Frank Christopher Howarth, Yaroslav M. Shuba, Murat Oz

Research output: Contribution to journalArticle

Abstract

A role for anandamide (N-arachidonoyl ethanolamide; AEA), a major endocannabinoid, in the cardiovascular system in various pathological conditions has been reported in earlier reports. In the present study, the effects of AEA on contractility, Ca2+ signaling, and action potential (AP) characteristics were investigated in rat ventricular myocytes. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the fluorescent indicator fura-2 AM. AEA (1μM) caused a significant decrease in the amplitudes of electrically evoked myocyte shortening and Ca2+ transients. However, the amplitudes of caffeine-evoked Ca2+ transients and the rate of recovery of electrically evoked Ca2+ transients following caffeine application were not altered. Biochemical studies in sarcoplasmic reticulum (SR) vesicles from rat ventricles indicated that AEA affected Ca2+-uptake and Ca2+-ATPase activity in a biphasic manner. [3H]-ryanodine binding and passive Ca2+ release from SR vesicles were not altered by 10μM AEA. Whole-cell patch-clamp technique was employed to investigate the effect of AEA on the characteristics of APs. AEA (1μM) significantly decreased the duration of AP. The effect of AEA on myocyte shortening and AP characteristics was not altered in the presence of pertussis toxin (PTX, 2μg/ml for 4h), AM251 and SR141716 (cannabinoid type 1 receptor antagonists; 0.3μM) or AM630 and SR 144528 (cannabinoid type 2 receptor antagonists; 0.3μM). The results suggest that AEA depresses ventricular myocyte contractility by decreasing the action potential duration (APD) in a manner independent of CB1 and CB2 receptors.

Original languageEnglish (US)
Pages (from-to)104-118
Number of pages15
JournalCell Calcium
Volume55
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Anandamide
  • Contraction
  • Endocannabinoid
  • Intracellular calcium
  • Ventricular action potential
  • Ventricular myocytes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Al Kury, L. T., Voitychuk, O. I., Ali, R. M., Galadari, S., Yang, K. H. S., Howarth, F. C., Shuba, Y. M., & Oz, M. (2014). Effects of endogenous cannabinoid anandamide on excitation-contraction coupling in rat ventricular myocytes. Cell Calcium, 55(2), 104-118. https://doi.org/10.1016/j.ceca.2013.12.005