title: Inhibitory effects of endocannabinoid on the action potential of pacemaker cells in sinoatrial nodes of rabbits.
abstract: Endocannabinoid anandamide (AEA) has protective effect on the heart against ischemia/reperfusion injury and arrhythmia, but the electrophysiological mechanism is unclear yet. In this study, the sinoatrial node (SAN) samples from New Zealand rabbits were prepared, and intracellular recording technique was used to elucidate the effect of AEA on the action potential (AP) of SAN pacemaker cells of rabbits and the mechanism. Different concentrations of AEA (1, 10, 100, 200, 500 nmol/L) were applied cumulatively. For some SAN samples, cannabinoid type 1 (CB1) receptor antagonist AM251, cannabinoid type 2 (CB2) receptor antagonist AM630, potassium channel blocker tetraethylammonium (TEA) and nitric oxide (NO) synthase inhibitor L-nitro-arginine methylester (L-NAME) were used before AEA treatment, respectively. We found that: (1) AEA (100, 200 and 500 nmol/L) not only shortened AP duration (APD), but also decreased AP amplitude (APA) (P < 0.05). (2) AM251, but not AM630, abolished the effect of AEA on APD shortening. (3) TEA and L-NAME had no influence on the AEA effect. These findings suggest that anandamide can decrease APA and shorten APD in SAN pacemaker cells of rabbits, which may be mediated by activation of CB1 receptors, and is related to blockade of calcium channels but not potassium channels and NO.
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
authors.forename: San-Yi
authors.initials: SY
authors.lastname: Wang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000200:Action Potentials; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology*
chemical_list: D001095:Arachidonic Acids; D063387:Cannabinoid Receptor Antagonists; D063388:Endocannabinoids; D007211:Indoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D009569:Nitric Oxide; C103505:AM 251; C094023:iodopravadoline; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester