The Cytoprotective Action of the Potassium Channel Opener BMS-191095 in C2C12 Myoblasts is Related to the Modulation of Calcium Homeostasis

Cellular Physiology and Biochemistry

关键词: Calpains;    Calcium;    Mitochondria;    Potassium channel opener BMS-191095;    Cytoprotection;   

DOI  :  10.1159/000320523

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

BMS-191095 is an opener of the mitochondrial ATP-regulated potassium channel, which has been shown to provide cytoprotection in models of ischemia-reperfusion induced injury in various tissues. This study aimed at checking the protective action of BMS-191095 under the conditions of oxidative stress or disruption of intracellular calcium homeostasis. Methods The cytoprotective potential of BMS-191095 was tested in C2C12 myoblasts injured by treatment with H₂O₂ or calcium ionophore A23187. The influence of the opener on intracellular calcium levels, calpain activity and respiration rates were determined. Results BMS-191095 protected myoblasts from calcium ionophore A23187-induced injury, but not from H H₂O₂-induced injury. A23187-mediated cell damage was also prevented by calpain inhibitor PD 150606. A23187 administration led to a transient increase in cytosolic calcium levels, concomitant activation of calpains and a decrease in state 3 respiration rates, indicating mitochondrial dysfunction. Co-administration of BMS-191095 diminished calpain activation in A23187-treated cells but did not prevent mitochondrial damage. In the presence of BMS-191095, restoration of cytosolic calcium concentrations to basal levels after A23187 treatment was considerably faster which may underly the reduced activation of calpains. Conclusion The BMS-191095-mediated cytoprotection observed in C2C12 myoblasts results probably from modulation of intracellular calcium transients leading to prevention of calpain activation.

【 授权许可】

CC BY-NC-ND