[Superoxide anion radical selectively increases Ca2+ release from cardiac sarcoplasmic reticulum through ryanodine receptor Ca2+ channel].
Because the net Ca2+ uptake in the sarcoplasmic reticulum (SR) of cardiac muscle is a result of the activity of Ca(2+)-ATPase and of the SR Ca(2+)-release channel, an abnormal Ca2+ uptake may be the result of the dysfunction of either or both structures. The site or sites of action for oxygen-derived free radicals (OFR) damage are unknown, although previous studies on the SR have focused on damage to the Ca2+ pump. Direct effects of OFR on SR Ca(2+)-release channels may be important in understanding their potential contribution to myocardial ischemia/reperfusion injury. We confirmed that superoxide anion radical (O2.-) generated from hypoxanthine-xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles. Electron spin resonance study showed that hydroxyl radicals are generated in addition to O2.- from hypoxanthine-xanthine oxidase reaction, and data indicate that O2.- is responsible for the observed effect. Current fluctuations through single Ca(2+)-release channels have been also monitored after incorporation into planar phospholipid bilayers. We directly demonstrate that activation of the channel by O2.- stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O2.-.
Okabe
E
E
Department of Pharmacology, Kanagawa Dental College, Japan.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002147:Calmodulin / Q000502:physiology; D004285:Dogs; D004578:Electron Spin Resonance Spectroscopy; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology*
D015220:Calcium Channels; D002147:Calmodulin; D013481:Superoxides; D000252:Calcium-Transporting ATPases; D002118:Calcium