CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Sarcoplasmic reticulum Ca2+ release channel (RyR2) cross-linking during reperfusion of ischemic heart: a possible pro-arrhythmogenic mechanism?
Autor/es:
BARBARA S. ROMAN; MARGARITA SALAS; MATILDE SAID; JUAN IGNACIO MARIANGELO; CECILIA MUNDIÑA-WEILENMANN; BECERRA ROMINA; LETICIA B. VITTONE
Lugar:
Rio de Janeiro
Reunión:
Congreso; XXXVIII IUPS Congress; 2017
Institución organizadora:
International Union of Physiological Sciences (IUPS)
Resumen:
Introduction: Arrhythmias of ventricular origin carry the greatest risk of sudden death. Those occurring during early reperfusion in post-ischemic hearts have been related to CaMKII phosphorylation of RyR2, SR Ca2+ leak and rhythm alterations. Experiments of ischemia reperfusion (I/R) in transgenic mice lacking CaMKII phosphorylation site on RyR2 showed that this phosphorylation, was necessary but not sufficient to explain the genesis of reperfusion arrhythmias. Since ROS are involved in I/R injury and RyR2 is a well-known redox sensor, we studied the impact of RyR2 oxidative modifications on these rhythm alterations. Different thiol oxidations can occur at the level of RyR2: S-nitrosylation, S-glutathionylation and disulphide oxidation. We found that S-nitrosylation and S-glutathionylation protect rather than promote the appearance of arrhythmias. Recently redox-mediated formation of disulphide bonds between two RyR2 subunits (cross-linking) was reported to increase channel activity in isolated myocytes. The aim of the present study was to search for the presence of this RyR2 modification in our I/R model.Methods: Langendorff perfused rat hearts were submitted to global ischemia (20min)/reperfusion (1 or 3min). Epicardial monophasic action potentials, mechanical parameters and RyR2 cross-linking, assessed by Western blot in non-reducing conditions, were examined.Results: Hearts submitted to I/R showed an increase in RyR2 cross-linking with respect to control untreated perfused hearts at 1 min reperfusion (8.48±1.50 vs. 4.16±1.26 % of total RyR2, n=6-8, p