Sarcoplasmic reticulum (SR) calcium release restitution vs increased calcium sequestration in the determination of calcium-induced cardiac arrhythmias.

MAZZOCCHI, GABRIELA; CELY ORTIZ, ALEJANDRA; FEDERICO, MARILÉN; FELICE, JUAN IGNACIO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

10 Sociedades Científicas: SAIC-SAIB-SAI-SAA-SAB-SAB-SAFE-SAFIS-SAH-SAP.

Following the discharge of Ca from the SR, the release mechanism enters a refractory period when it is unresponsive to stimulation by cytosolic Ca. The time elapsed between two consecutive full Ca releases is known as Ca release restitution (CRR). Interventions that accelerate or slow SR refilling, accelerate or slow CRR, respectively. CRR is significantly hastened in post-infarction myocytes thereby accounting for increased vulnerability of these myocytes to diastolic spontaneous arrhythmogenic Ca waves and arrhythmias. Hypothesis: Acceleration of CRR is associated with an increase in stress?induced arrhythmias. Methods: Wild-type mice (WT), knock-in mice with constitutive pseudo-phosphorylation of RyR2 at Ser2814 site of CaMKII (S2814D) and increased SR Ca leak, and SDKO mice resultant from crossbreeding phospholamban ablated mice (PLNKO), with increased velocity of SR Ca sequestration, and S2814D were used. We estimated Ca transients and SR Ca load with fluorescent dyes and used confocal microscopy to determine diastolic SR Ca leak. Restitution curves were obtained by introducing an additional stimulation pulse at different time intervals with respect to the regular pacing pulses. Results: Compared to WT, S2814D have accelerated CRR (174±6.2 vs. 235±11.4 msec, p