Effect on L-type calcium channel autoinhibition during myocardial ischemia-reperfusion injury
Xia Bing
Li Xinru
Xi Hong
Chen Jiannan
Yang Lingyu
Li Xuewen
Yue Zhijie
Abstract：Objective To investigate the effect of myocardial ischemia-reperfusion(I/R)injury on the autoinhibition function of L-type calcium channels(L-VDCC)and its mechanism.Methods Isolated rat hearts were perfused to establish I/R model.The changes of cardiac function after I/R were monitored by BL-420 N biological signal acquisition and analysis system.CoCl2 was used to cause hypoxia damage in acutely isolated rat cardiomyocytes to construct a cell I/R model.The function of L-VDCC was detected by patch clamp technique,Co-IP and Western Blot analysis.Results Compared with the ischemia 0 min group and ischemia 30 min group,the ischemia 60 min group showed reduced cardiac contractility and weakened myocardial electrical activity after reperfusion.Compared with the hypoxia 0 h group,the peak of the current-voltage(I-V)curve of L-VDCC in the hypoxia 6 h and hypoxia 12 h groups increased,the steady-state activation curve shifted left,the half-activation voltage(V1/2)increased,the slope factor Ka of the steady-state activation curve decreased,and cell death rate increased;the amount of Cav1.2 binding to DCT and CaM decreased,with all differences being statistically significant(P<0.05);there were no significant changes in the expression levels of exogenous regulatory proteins such as PKA and PKG.Conclusion Myocardial I/R injury can weaken the autoinhibition function of myocardial cell L-VDCC,increase Ca2+inflow,cause cell calcium overload,and promote myocardial cell death.
Keywords：Ischemia-reperfusion injuryCalcium overloadL-type voltage-dependent calcium channelAutoinhibitionCardiac
Publication Date：2024-05-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 586-592 )