Myocardial ischemia-reperfusion induces intersubunit cross-linking in calcium release channel (RyR2).

SILVESTRI A; MARIÁNGELO JIE; MUNDIÑA -WEILENMANN C; BECERRA R; VITTONE L; SAID M; ROMAN B; SALAS M

Mar del Plata

Congreso; Reunión conjunta SAI SAFIS SAIC; 2018

Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina de Fisiología (SAFIS)

Restoration of coronary flow after myocardial ischemia (I/R) although necessary, can lead to adverse effects such as ventricular arrhythmias attributed to increased RyR2 activity. Experiments from our laboratory showed that complete prevention of oxidative stress decreases the reperfusion arrhythmias. Since the selective inhibition of S-nitrosylation and S-glutathionylation, two oxidative modifications of RyR2, did not attenuate the ventricular arrhythmogenesis other oxidative RyR2 modifications should be involved in the generation of these rhythm alterations. Recently, the increase in the channel activity by redox-mediated formation of disulphide bonds between two RyR2 subunits (cross-linking, XL) was reported. Aim: To identify RyR2-XL of formation during the I/R protocol and its possible correlation with arrhythmic activity Methods: Langendorff perfused rat hearts were subjected to I/R (20/1-3min), in the presence or absence of a non-specific ROS scavenger, MPG (2mM). Epicardial monophasic action potentials, mechanical parameters and RyR2-XL (assessed by Western Blot) were examined. Results: Hearts submitted to I/R showed an increase in ventricular premature beats (VPB) 51 ± 4 with respect to non-ischemic hearts (Ctrl), 3 ± 2 (n = 5-6, p