Ischemic Preconditioning (PC) increases the activity of RyR2 in the myocardium

SAID M. M., BECERRA R., SÁNCHEZ G., DONOSO P., MUNDIÑA- WEILENMANN C., MATTIAZZI A., VITTONE L.

Hotel Sheraton, Bs. As., Argentina

Congreso; International Society for Heart Research, XVII Meeting Latin American Section; 2009

International Society for Heart Research, Latin American Section

Ischemic preconditioning (PC) activates cardioprotection by mechanisms not fully understood. A brief and transient increase in Ca2+i during PC is proposed to be a trigger for cardioprotection. We studied the possible involvement of RyR2 in this increase in Ca2+i during the PC period. Langerdorff perfused rat hearts (4Hz, 37º) were submitted to 1 period of 5min global ischemia, followed by 1min reperfusion, a protocol proved to induce PC. After 1min reperfusion, we measured [3H]-ryanodine binding, CaMKII-dependent phosphorylation and S-glutathionylation of RyR2 and NADPH oxidase activity in isolated sarcoplasmic reticulum membranes from these hearts.  We found a 2-fold increase in RyR2 S-glutathionylation with no change in CaMKII-dependent phosphorylation at Ser 2815 in PC compared to hearts without ischemia (C). PC also increased [3H]-ryanodine binding from 0.15±0.03, n=9 (C) to 0.32±0.02, n=7 (PC) pmol/mg protein and NADPH oxidase activity from 2.1±0.8, n=17 (C) to 4.4±2.2, n=6 (PC) nmol O2.-/mg protein/min. These results suggest that PC increases the activity of RyR2 through redox modifications without changes in CaMKII-dependent phosphorylation.  The increase in RyR2 activity could explain the brief and transient increase in Ca2+i during PC.