Abstract
A stilbene derivative, DIDS, suppresses staurosporine (STS)-induced apoptosis in many cell types. However, it has not been clarified which is the target of DIDS in apoptosis of cardiomyocytes, Cl−/HCO3− exchangers or Cl− channels. To answer this question, we examined STS-induced reduction of cell viability, DNA laddering and caspase-3 activation using cultured mouse ventricular myocytes in the presence or absence of HCO3−. STS-induced apoptosis and its DIDS sensitivity in HCO3−-free conditions were indistinguishable from those in HCO3−-rich conditions. Apoptosis was also prevented by application of another Cl− channel blocker, NPPB, which cannot block Cl−/HCO3− exchangers. These data rule out contribution of Cl−/HCO3− exchanger in cardiomyocyte apoptosis and its DIDS sensitivity. Cardiomyocytes derived from ClC-3-deficient mice similarly underwent apoptosis after exposure to STS. Application of DIDS or NPPB prevented STS-induced apoptosis in ClC-3-deficient cardiomyocytes. Thus, we conclude that apoptosis in cardiomyocytes is critically dependent on the activity of Cl− channel which is distinct from ClC-3, but not of Cl−/HCO3− exchangers. [Jpn J Physiol 55 Suppl:S75 (2005)]
