Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei, China.
Br J Pharmacol. 2009 Dec;158(8):2022-9. doi: 10.1111/j.1476-5381.2009.00518.x.
The endocannabinoid, anandamide, has anti-arrhythmic effects. The aim of the present study was to explore the electrophysiological effects of anandamide on rat myocardium.
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.
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.
These data suggest that anandamide suppressed AP and L-type Ca2+ current in cardiac myocytes through CB1 receptors.
内源性大麻素，大麻素，具有抗心律失常作用。本研究旨在探讨大麻素对大鼠心肌的电生理作用。
采用细胞内记录技术在大鼠心肌乳头肌中记录诱发动作电位（APs）。此外，采用全细胞膜片钳记录技术在分离的大鼠心室肌细胞中测量和分析 L 型钙电流。
在心肌乳头肌中，大麻素（1、10、100 nM）以浓度依赖性方式降低 AP 持续时间。此外，100 nM 大麻素降低部分去极化乳头肌中的 AP 幅度、超射和 Vmax。这些作用被 CB1 受体的选择性拮抗剂 AM251（100 nM）而不是 CB2 受体拮抗剂 AM630（100 nM）所消除。此外，L 型钙通道激动剂 Bay K 8644（0.5 μM）、钾通道阻断剂四乙铵（20 mM）和一氧化氮合酶抑制剂 L-NAME（1 mM）对大麻素诱导的 AP 持续时间缩短没有影响。在分离的心室肌细胞中，大麻素（1、10、100 nM）浓度依赖性地降低 L 型钙电流，并使钙电流的电流-电压关系曲线发生位移。大麻素（100 nM）使稳态失活曲线向左移位，恢复曲线向右移位。用 AM251（100 nM）阻断 CB1 受体，但用 AM630（100 nM）阻断 CB2 受体，消除了大麻素对 L 型钙电流的作用。
这些数据表明，大麻素通过 CB1 受体抑制心肌细胞中的 AP 和 L 型钙电流。
