Electrophysiological effects of anandamide on rat myocardium.
OBJECTIVE
The endocannabinoid, anandamide, has anti-arrhythmic effects. The aim of the present study was to explore the electrophysiological effects of anandamide on rat myocardium.


METHODS
Evoked action potentials (APs) were recorded using intracellular recording technique in rat cardiac papillary muscles. In addition, L-type Ca2+ current was measured and analysed using whole-cell patch-clamp recording technique in isolated rat cardiac ventricular myocytes.


RESULTS
In cardiac papillary muscles, anandamide (1, 10, 100 nM) decreased AP duration in a concentration-dependent manner. Furthermore, 100 nM anandamide decreased AP amplitude, overshoot and Vmax in partially depolarized papillary muscles. These effects were abolished by AM251 (100 nM), a selective antagonist for CB1 receptors, but not AM630 (100 nM), a CB2 receptor antagonist. Furthermore, an agonist of L-type Ca2+ channels, Bay K 8644 (0.5 microM), a K+ channel blocker tetraethylammonium chloride (20 mM) and the nitric oxide synthase inhibitor L-NAME (1 mM) had no effect on anandamide-induced decrease in AP duration. In isolated ventricular myocytes, anandamide (1, 10, 100 nM) decreased L-type Ca2+ current concentration-dependently, and shifted the current-voltage relationship curve of the Ca2+ current. Anandamide (100 nM) shifted the steady-state inactivation curve to the left and the recovery curve to the right. Blockade of CB1 receptors with AM251 (100 nM), but not CB2 receptors with AM630 (100 nM), eliminated the effect of anandamide on L-type Ca2+ currents.


CONCLUSIONS
These data suggest that anandamide suppressed AP and L-type Ca2+ current in cardiac myocytes through CB1 receptors.
Li
Qian
Q
Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei, China.
Ma
Hui-Jie
HJ
Zhang
Hao
H
Qi
Zhao
Z
Guan
Yue
Y
Zhang
Yi
Y
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D063388:Endocannabinoids; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide