TY - JOUR
T1 - Effects of endogenous cannabinoid anandamide on excitation-contraction coupling in rat ventricular myocytes
AU - Al Kury, Lina T.
AU - Voitychuk, Oleg I.
AU - Ali, Ramiz M.
AU - Galadari, Sehamuddin
AU - Yang, Keun Hang Susan
AU - Howarth, Frank Christopher
AU - Shuba, Yaroslav M.
AU - Oz, Murat
N1 - Funding Information:
This study was supported by the United Arab Emirates University Research Funds. Research in our laboratory is also supported by LABCO partner of Sigma–Aldrich. We cordially thank Mr. Muhammad A. Qureshi for his technical help in myocyte isolation and myocyte shortening experiments. This article has been submitted to fulfill in part the thesis requirements for Ms. Lina Al Kury.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - Anandamide
KW - Contraction
KW - Endocannabinoid
KW - Intracellular calcium
KW - Ventricular action potential
KW - Ventricular myocytes
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U2 - 10.1016/j.ceca.2013.12.005
DO - 10.1016/j.ceca.2013.12.005
M3 - Article
C2 - 24472666
AN - SCOPUS:84893953431
SN - 0143-4160
VL - 55
SP - 104
EP - 118
JO - Cell Calcium
JF - Cell Calcium
IS - 2
ER -