Increased Ca2+ reuptake into cardiac sarcoplasmic reticulum transform the arrhythmogenic Ca2+ waves into a new profile of spontaneous Ca2+ release.

VALVERDE CA; RAGONE I; MATTIAZZI A; MAZZOCCHI G; CONSOLINI A; FELICE J; PORTIANSKY E

Rio de Janeiro

Congreso; 38th World Congress of the International Union of Physiological Sciences (IUPS) ? Rhythms of Life ?; 2017

International Union of Physiological Sciences

Thecytosolic Ca2+ waves are arrhythmogenic and are produce due to aspontaneous Ca2+ release via the sarcoplasmic reticulum (SR)ryanodine receptors (RyR2), in Ca2+ overload conditions, whichphosphorylates Ser2814-RyR2. Ca2+ released through a RyR2cluster can diffuse to a neighbor cluster inducing another Ca2+release (Ca2+ wave propagation mechanism). During reperfusion of theischemic heart (I/R), said waves are exacerbated and constitute the mainmechanism of reperfusion arrhythmias which involves sodium/calcium exchangeractivity. Our hypothesis is that the increase in SR Ca2+ reuptake (phospholamban(PLN) ablation) diminishes reperfusion arrhythmias by transforming Ca2+waves into non-propagated, non-arrhythmogenic events (mini-waves). With the aidof intracellular microelectrodes we assessed action potentials in intact heartssubmitted to I/R, and using confocal microscopy we evaluated the spontaneous SRCa2+ release events during I/R. The results indicated thatincreasing SR Ca2+ uptake diminishes reperfusion arrhythmias andfully-propagated Ca2+ waves. Indeed, non-propagated events increaseits frequency, which most of them were of intermediate magnitude between theclassic Ca2+ miniwaves and Ca2+ sparks, like a series ofmini-events (like necklace beads) keeping the front profile of a wave. These Ca2+necklace beads events were visualized as alternating raises and reductions influorescence. By contrast, PLN ablation exacerbated reperfusion-inducedmitochondria damage due to exacerbated Ca2+ leak from SR. Conclusion:Our results indicate that increasing SR Ca2+ reuptake contributes inpreventing reperfusion arrhythmias by transforming Ca2+ waves intonon-propagated events. However, it cannot prevent cardiac damage produced by CaMKII-dependentphosphorylation of RyR2.