Impact of post-translational modifications of cardiac ryanodine receptor (RyR2) on reperfusion arrhythmias

SAID M; BECERRA R; HERRERO A; TELLECHEA M; MUNDIÑA-WEILENMANN C; MATTIAZZI A.; VITTONE L.

Santiago

Congreso; XX Anual Meeting of the International Societe for Heart Research Latin American Section; 2012

International Society for Heart Research Latin American Section

Reperfusion (R) after ischemia is particularly prone to cardiac arrhythmias. This work investigated the role of redox modifications and CaMKII-dependent phosphorylation (Ser2815 residue) of RyR2 upon arrhythmias appearance. Langendorff perfused rat/mouse hearts were submitted to global ischemia/reperfusion. Epicardialmonophasic action potentials and left ventricular developed pressure were recorded. Premature beats (PB) were counted during R in the absence or the presence of inhibitors: 10 μM APO (NADPHox), 10 μM L-Name (NOS) and 2.5 μM KN-93 (CaMKII). At the onset of R, S-glutathionylation (SGLU), S-nitrosylation (S-SNO) and Ser2815 phosphorylation of RyR2 increased. APO significantly decreased S-GLU of RyR2 and increased PB from 42±4 to 59±3. L-Name did not modify PB and KN-93 significantly decreased both Ser2815 phosphorylation and PB to 13± 3. The results suggest that CaMKII-phosphorylation of RyR2 at the onset of R favours arrhythmias, whereas S-GLU-RyR2 may partially prevent them. It would be interesting to explore if the spontaneous SR Ca2+ leak induced by phosphorylation, main mechanism responsible for arrhythmias, is limited by S-GLU-RyR2.