Antisense inhibition of Na+/Ca2+ exchange during anoxia/reoxygenation in ventricular myocytes

This study investigated the role of the Na+/Ca2+ exchanger (NCX) in regulat ing cytosolic intracellular Ca2+ concentration ([Ca2+](i)) during anoxia/re oxygenation in guinea pig ventricular myocytes. The hypothesis that the NCX is the predominant mechanism mediating [Ca2+](i) overload in this model wa s tested through inhibition of NCX expression by an antisense oligonucleoti de. Immunocytochemistry revealed that this antisense oligonucleotide, direc ted at the area around the start site of the guinea pig NCX1, specifically reduced NCX expression in cultured adult myocytes by 90 +/-4%. Antisense tr eatment inhibited evoked NCX activity by 94 +/-3% and decreased the rise in [Ca2+](i) during anoxia/reoxygenation by 95 +/-3%. These data suggest that NCX is the predominant mechanism mediating Ca2+ overload during anoxia/reo xygenation in guinea-pig ventricular myocytes.