Department of Pharmacology, Huazhong University of Science and Technology, Wuhan, China.
Am J Chin Med. 2010;38(1):37-49. doi: 10.1142/S0192415X1000766X.
Our previous studies have shown that daurisoline (DS) exerted antiarrhythmic effects on various experimental arrhythmias. In this study, the effects of DS on early afterdepolarizations (EADs) and its possible mechanisms have been investigated. Cardiac hypertrophy was induced in rabbits by coarctating the abdominal aorta. The effects of DS on action potential duration (APD) and the incidences of EADs were studied in hypertrophied papillary muscles of rabbits in the conditions of low external K(+) concentration ([K(+)]o) and dofetilide (dof) by using standard microelectrode technique. The whole-cell patch clamp was used to record the L-type calcium current (I(Ca-L)) in isolated left ventricular cells of rabbits. The results showed that in hypertrophied papillary muscles of rabbits with low [K(+)]o ([K(+)]o = 2.7 mM), 1 microM dof prolonged APD(50) and APD(90) markedly and the incidence of EADs was 66.7% (4/6, p < 0.01); when 15 microM DS was applied, the incidence of EADs was 0% (0/4, p < 0.01) and the prolonged APD was shortened (p < 0.01). In a single myocyte, DS could also inhibit EADs induced by dof, low [K(+)]o and low external Mg(2+) concentration ([Mg(2+)]o) (Mg(2+) = 0.5 mM). DS could decrease the triangulation. In a single myocyte, DS could make the I-V curve upward, shift the steady-state activation curves to the right and the steady-state inactivation curves to the left and prolong the tau value of recovery curve obviously. These results suggested that DS could inhibit EADs which may be associated with its blockade effects on I(Ca-L).
我们之前的研究表明，daurisoline（DS）对各种实验性心律失常具有抗心律失常作用。在这项研究中，研究了 DS 对早期后除极（EAD）的影响及其可能的机制。通过缩窄腹主动脉在兔中诱导心肌肥厚。使用标准微电极技术，在低细胞外 K（+）浓度（[K（+）] o）和多非利特（dof）的条件下，研究了 DS 对兔肥厚乳头肌动作电位时程（APD）和 EAD 发生率的影响。使用全细胞膜片钳记录兔左心室细胞的 L 型钙电流（I（Ca-L））。结果表明，在低 [K（+）] o（[K（+）] o = 2.7 mM）的兔肥厚乳头肌中，1 microM dof 明显延长 APD（50）和 APD（90），EAD 的发生率为 66.7%（4/6，p < 0.01）；当应用 15 microM DS 时，EAD 的发生率为 0%（0/4，p < 0.01），延长的 APD 缩短（p < 0.01）。在单个心肌细胞中，DS 还可以抑制由 dof、低 [K（+）] o 和低细胞外 Mg（2+）浓度（[Mg（2+）] o）（[Mg（2+）] o = 0.5 mM）引起的 EAD。DS 可以减小三角。在单个心肌细胞中，DS 可以使 I-V 曲线向上，将稳态激活曲线向右移动，将稳态失活曲线向左移动，并明显延长恢复曲线的 tau 值。这些结果表明，DS 可以抑制 EAD，这可能与其对 I（Ca-L）的阻断作用有关。
