HCO3--independent rescue from apoptosis by stilbene derivatives in rat cardiomyocytes

Apoptosis of rat cardiomyocytes induced by staurosporine is prevented by a stilbene derivative (DIDS), which is a known blocker of both Cl-/HCO3- exchangers and Cl− channels. To clarify its target, staurosporine-induced activation of caspase-3, DNA laddering and cell death were examined in cultured rat cardiomyocytes. Removal of ambient HCO3-, which minimizes the function of Cl-/HCO3- exchangers, failed to affect the preventive effect of DIDS on apoptosis. A carboxylate analog Cl− channel blocker, which does not block Cl-/HCO3- exchangers, also inhibited apoptotic events. Thus, rescue by DIDS of cardiomyocytes from apoptosis is mediated by blockage of Cl− channels.