Transient Ca2+ depletion of the sarcoplasmic reticulum at the onset of reperfusion.

VALVERDE C; KORNYEYEV D; FERREIRO M; PETROSKY AD; MATTIAZZI A

CARDIOVASCULAR RESEARCH

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2010 vol. 85 p. 671 - 680

0008-6363

Transient Ca2+ depletion of the sarcoplasmic reticulum at the onset of reperfusion. Valverde CA, Kornyeyev D, Ferreiro M, Petrosky AD, Mattiazzi A, Escobar AL. Facultad de Cs. Médicas, Centro de Investigaciones Cardiovasculares, UNLP, Conicet, La Plata, Argentina. Abstract AIMS: Myocardial stunning is a contractile dysfunction that occurs after a brief ischaemic insult. Substantial evidence supports that this dysfunction is triggered by Ca2+ overload during reperfusion. The aim of the present manuscript is to define the origin of this Ca2+ increase in the intact heart. METHODS AND RESULTS: To address this issue, Langendorff-perfused mouse hearts positioned on a pulsed local field fluorescence microscope and loaded with fluorescent dyes Rhod-2, Mag-fluo-4, and Di-8-ANEPPS, to assess cytosolic Ca2+, sarcoplasmic reticulum (SR) Ca2+, and transmembrane action potentials (AP), respectively, in the epicardial layer of the hearts, were submitted to 12 min of global ischaemia followed by reperfusion. Ischaemia increased cytosolic Ca2+ in association with a decrease in intracellular Ca2+ transients and a depression of Ca2+ transient kinetics, i.e. the rise time and decay time constant of Ca2+ transients were significantly prolonged. Reperfusion produced a transient increase in cytosolic Ca2+ (Ca2+ bump), which was temporally associated with a decrease in SR-Ca2+ content, as a mirror-like image. Caffeine pulses (20 mM) confirmed that SR-Ca2+ content was greatly diminished at the onset of reflow. The SR-Ca2+ decrease was associated with a decrease in Ca2+ transient amplitude and a shortening of AP duration mainly due to a decrease in phase 2. CONCLUSION: To the best of our knowledge, this is the first study in which SR-Ca2+ transients are recorded in the intact heart, revealing a previously unknown participation of SR on cytosolic Ca2+ overload upon reperfusion in the intact beating heart. Additionally, the associated shortening of phase 2 of the AP may provide a clue to explain early reperfusion arrhythmias.