MG53 Downregulates The Expression Of KChIP2,an Outward Potassium Channel Subunit,by Modulating NF-κB Signaling During Myocardial Infarction

AIM:Ischemia and hypoxia caused transient outward potassium channel downregulation,prolonged action potential duration and caused arrhythmia,but the mechanism is not yet clear.In this study,we had established hypoxic cardiomyocyte model and myocardial infarction mouse model.We analyzed transient outward K⁺channels subunits and mechanism by cellular and molecular biology methods.Besides,the study also explored the relationship between transient outward potassium channel and MG53 in myocardial ischemia/hypoxia.The role and mechanisms of MG53 in myocardial ischemia/hypoxia also had been studied.RESULTS:（1）the expression of MG53 and transient outward potassium currents(I_to,Both theαsubunit Kv4.3 and theβsubunit KChIP2)in both neonatal rats（hypoxia 4h）and adult mice（myocardial infarction 48h）or human cardiomyocytes decreased（p<0.05）.（2）Overexpression/down-regulation of MG53 at the cellular level can affect I_to,fo,f current density（p<0.05）.（3）Overexpression/down-regulation of MG53 can regulate the expression of KChIP2 by NF-κB signaling pathway（p<0.05）.（4）MG53 did not activate the MAPK pathway.（5）MG53 overexpression treatment can alleviate the transient outward potassium ionβsubunit caused by hypoxia（p<0.05）.CONCLUSION:As a skeletal and cardiac-specific membrane repair protein,MG53 can decease KChIP2 and I_to,f expression by activating NF-κB signaling pathway,with a result of arrhythmia.Overexpression of MG53 attenuates the decrease of KCh IP2 and I_to,f current density by inhibiting NF-κB pathway.These results indicated that MG53 can inhibit arrhythmia.