ISCHEMIC PRECONDITIONING (PC) INCREASES THE ACTIVITY OF RYR2 IN THE MIOCARDYUM

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

Ciudad Autónoma de Buenos Aires, Argentina

Congreso; XVIII Meeting of ISHR 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 Cai 2+ during PC is proposed to be a trigger for cardioprotection. We studied the possible involvement of RyR2 in this increase in Cai 2+. Langendorff perfused rat hearts (4 Hz, 37 °C) were submitted to 1 period of 5-min global ischemia, followed by 1-min reperfusion, a protocol proved to induce PC. After 1-min reperfusion, we measured [3H]ryanodine binding, CaMKII-dependent phosphorylation and Sglutathionylation 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 CaMKIIdependent phosphorylation at Ser2815 in PC compared to heart without ischemia (control, 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 Cai2+ during PC.