Intracellular Ca2+ dynamics in ischemia/reperfusion

MATTIAZZI A

Santiago

Simposio; XX Reunión Anual Sección Latinoamericana de la International Society for Heart Research (ISHR; 2012

ISHR

We previously demonstrated the beneficial effect of calciumcalmodulin-dependent protein kinase (CaMKII) phosphorylation of sarcoplasmic reticulum (SR) proteins at the onset of reperfusion, after a relatively short ischemic period [stunned heart, (Am J Physiol., 2003)]. We recently showed however, that CaMKII-dependent phosphorylation of SR proteins is also detrimental, since it contributes to reperfusion arrhythmias (J Mol Cell Cardiol, 2011). Now, the critical question is: which are the mechanisms that link the increase in CaMKII-dependent phosphorylation of SR proteins with either a beneficial or detrimental effect in I/R? A necessary step to answer this paradox is to explore Ca2+ dynamics at the cytosol and SR during I/R. We used Pulsed Local Field Fluorescence microscopy, for simultaneous determination of SR and cytosolic Ca2+ and mechanical parameters, and confocal microscopy to study Ca2+sparks and waves during I/R, in the intact heart. The results indicate that CaMKII dependent phosphorylation of phospholamban at the onset of reperfusion is a main responsible for the recovery of intracellular Ca2+ transient. These findings support the beneficial effect of CaMKII on contractility during reperfusion. Moreover, the increase in CaMKII dependent phosphorylation of RyR2 at the onset of reperfusion is associated with an abrupt increase in cytosolic Ca2+ released by the SR and an increase in Ca2+ waves. These events may constitute the underlying mechanism of the detrimental effect of CaMKII in I/R, i.e. the observed CaMKII-dependent reperfusion triggered arrhythmias.