Carbon monoxide protects cardiomyogenic cells against ischemic death through L-type Ca2+ channel inhibition.
Carbon monoxide (CO) is known to protect myocardial and vascular cells against injuries due to ischemia-reperfusion or inflammation. We showed that a Ca(2+)-dependent protease calpain promotes necrotic cell death of cardiomyocyte-derived H9c2 cells due to hypoxia through alpha-fodrin proteolysis. Here, we show that ischemia induces necrotic cell death, which is inhibited by either CO, extracellular Ca(2+) deprivation or L-type Ca(2+) channel blockers. A whole cell patch-clamp experiment supports that CO inhibits L-type Ca(2+) channel mediated influx of Ca(2+) and the ischemic death of H9c2 cells.
Uemura
Koichi
K
Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. kuemura@m.u-tokyo.ac.jp
Adachi-Akahane
Satomi
S
Shintani-Ishida
Kaori
K
Yoshida
Ken-ichi
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002245:Carbon Dioxide / Q000008:administration & dosage*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D017202:Myocardial Ischemia / Q000473:pathology* / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
D020746:Calcium Channels, L-Type; D002245:Carbon Dioxide; D002118:Calcium