背景:心血管疾病仍然是全球死亡的主要原因之一。心肌缺血和梗塞,特别是,经常引起心脏电活动紊乱,从而引发室性心律失常。我们的目的是调查儿茶素,内源性儿茶酚胺抑制肽,改善大鼠心肌缺血引起的室性心律失常及其潜在的离子机制。
结果:成年雄性SD大鼠随机分为对照组和儿茶素组。结扎左冠状动脉前降支并电刺激可诱发室性心律失常。动作电位,瞬态外向钾电流,延迟整流钾电流,向内整流钾电流,使用膜片钳技术记录大鼠心室肌细胞的L型钙电流(ICa-L)。Catestin显著减轻了大鼠心肌缺血/再灌注和电刺激引起的室性心律失常。在心室肌细胞中,儿茶素显著缩短心室肌细胞的动作电位持续时间,它被钾通道拮抗剂TEACl和4-AP所抵消,和ICa-L电流通道激动剂BayK8644。此外,儿茶素显著增加瞬时外向钾电流,延迟整流钾电流,并以浓度依赖的方式向内整流钾电流密度。Catestatin加速了瞬时外向钾电流通道的激活并减缓了失活。此外,儿茶素以浓度依赖性方式降低ICa-L电流密度。Catestatin还加速了ICa-L通道的失活,并减慢了ICa-L从失活中的恢复。
结论:Catestatin增强瞬时外向钾电流的活性,延迟整流钾电流,和向内整流钾电流,同时抑制心室肌细胞中的ICa-L,导致大鼠动作电位持续时间缩短,最终减少室性心律失常。
BACKGROUND: Cardiovascular disease remains one of the leading causes of death globally. Myocardial ischemia and infarction, in particular, frequently cause disturbances in cardiac electrical activity that can trigger ventricular arrhythmias. We aimed to investigate whether catestatin, an endogenous catecholamine-inhibiting peptide, ameliorates myocardial ischemia-induced ventricular arrhythmias in rats and the underlying ionic mechanisms.
RESULTS: Adult male Sprague-Dawley rats were randomly divided into control and catestatin groups. Ventricular arrhythmias were induced by ligation of the left anterior descending coronary artery and electrical stimulation. Action potential, transient outward potassium current, delayed rectifier potassium current, inward rectifying potassium current, and L-type calcium current (ICa-L) of rat ventricular myocytes were recorded using a patch-clamp technique. Catestatin notably reduced ventricular arrhythmia caused by myocardial ischemia/reperfusion and electrical stimulation of rats. In ventricular myocytes, catestatin markedly shortened the action potential duration of ventricular myocytes, which was counteracted by potassium channel antagonists TEACl and 4-AP, and ICa-L current channel agonist Bay K8644. In addition, catestatin significantly increased transient outward potassium current, delayed rectifier potassium current, and inward rectifying potassium current density in a concentration-dependent manner. Catestatin accelerated the activation and decelerated the inactivation of the transient outward potassium current channel. Furthermore, catestatin decreased ICa-L current density in a concentration-dependent manner. Catestatin also accelerated the inactivation of the ICa-L channel and slowed down the recovery of ICa-L from inactivation.
CONCLUSIONS: Catestatin enhances the activity of transient outward potassium current, delayed rectifier potassium current, and inward rectifying potassium current, while suppressing the ICa-L in ventricular myocytes, leading to shortened action potential duration and ultimately reducing the ventricular arrhythmia in rats.