Anti-arrhythmic effect mediated by regulation of κ-opioid receptor agonist U50,488H on Cx43 is associated with inhibition of calcium channel

Aim To investigate whether U50,488H(a selective κ-opioid receptor agonist) participates in the anti-arrhythmic effect mediated by κ-opioid receptor through inhibition of calcium channel and reduction of calcium influx.Methods 30 SD rats were randomly divided into 5 groups(6 rats in each group): control group(Con),ischemia group(Isc),ischemia+U50,488H group(Isc+U50),ischemia+U50,488H+Bay k8644(a calcium channel activator) group(Isc+U50+Bay),ischemia+Bay k8644 group(Isc+Bay).Models of acute myocardial ischemia were established by ligation of the left anterior descending coronary artery in the rats.U50,488H(1.5 mg·kg-1) and Bay k8644(66.7 μg·kg-1) were administered before the 30 min ischemia.Incidence of arrhythmia,changes of Connexin 43(Cx43) protein and mRNA expression in different groups were observed respectively.Results ① In rat models of acute myocardial ischemia,Bay k8644 reversed the anti-arrhythmic effect mediated by κ-opioid receptor stimulation with U50,488H(P0.05).② At the level of protein expression,Bay k8644 blocked the protective up-regulation of Cx43 conferred by U50,488H when ischemia occurred(P0.01).③ At the level of gene expression,Bay k8644 also reversed the stabilization of Cx43 mRNA mediated by κ-opioid receptor stimulation with U50,488H during ischemia(P0.01).Conclusion Through inhibition of calcium channel and reduction of calcium influx,U50,488H participates in the stabilization of Cx43 and anti-arrhythmic effect mediated by κ-opioid receptor when acute myocardial ischemia occurs.