title: ClC-3-independent sensitivity of apoptosis to Cl- channel blockers in mouse cardiomyocytes.
abstract: It has been shown that Cl-/HCO3- exchangers and Cl- channels, both of which are sensitive to stilbene derivatives, have essential roles in the mechanism of apoptosis induction. Staurosporine-induced apoptosis in neonatal mouse cardiomyocytes was prevented by a stilbene derivative, DIDS. To clarify whether Cl-/HCO3- exchangers or Cl- channels are targets of DIDS and whether ClC-3 is involved in the apoptotic process, staurosporine-induced reduction of cell viability, DNA laddering and caspase-3 activation were examined in cultured mouse ventricular myocytes derived from wild-type and ClC-3-deficient mice. Staurosporine-induced apoptosis and its DIDS sensitivity in ambient HCO3(-)-free conditions in which operation of Cl-/HCO3- exchangers is minimized were indistinguishable from when HCO3- was present. Apoptosis was also prevented by application of a non-stilbene-derivative Cl- channel blocker, NPPB, which cannot block Cl-/HCO3- exchangers. Cardiomyocytes derived from ClC-3-deficient mice similarly underwent apoptosis after exposure to staurosporine; moreover, apoptosis was prevented by application of DIDS or NPPB. Thus, we conclude that in cardiomyocytes, apoptosis is critically dependent on operation not of Cl-/HCO3- exchangers but of Cl- channels which are distinct from ClC-3.
authors.affiliation: Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tanabe
authors.forename: Hiromi
authors.initials: H
authors.lastname: Uramoto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Jishage
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uchida
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D009206:Myocardium / Q000166:cytology*; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; C115376:ClC-3 channel; D019311:Staurosporine