NBCe1 Na+-HCO3- cotransporter ablation causes reduced apoptosis following cardiac ischemia-reperfusion injury in vivo.

Abstract

AIMTo investigate the hypothesis that cardiomyocyte-specific loss of the electrogenic NBCe1 Na+-HCO3- cotransporter is cardioprotective during in vivo ischemia-reperfusion (IR) injury.METHODSAn NBCe1 (Slc4a4 gene) conditional knockout mouse (KO) model was prepared by gene targeting. Cardiovascular performance of wildtype (WT) and cardiac-specific NBCe1 KO mice was analyzed by intraventricular pressure measurements, and changes in cardiac gene expression were determined by RNA Seq analysis. Response to in vivo IR injury was analyzed after 30 min occlusion of the left anterior descending artery followed by 3 h of reperfusion.RESULTSLoss of NBCe1 in cardiac myocytes did not impair cardiac contractility or relaxation under basal conditions or in response to β-adrenergic stimulation, and caused only limited changes in gene expression patterns, such as those for electrical excitability. However, following ischemia and reperfusion, KO heart sections exhibited significantly fewer apoptotic nuclei than WT sections.CONCLUSIONThese studies indicate that cardiac-specific loss of NBCe1 does not impair cardiovascular performance, causes only minimal changes in gene expression patterns, and protects against IR injury in vivo .