Abstract
Membrane ionic currents (Im) measurement from cardiac multicellular preparations has been an obstacle in the understanding of cardiac excitability. The role of Na-Ca exchanger (NCX) in excitation-contraction coupling has remained elusive greatly due to this difficulty. Here we used loose patch photolysis to measure Im in intact-perfused whole hearts, to investigate the impact of the Ca2+ released from the sarcoplasmic reticulum (SR) on the epicardial action potential (AP). We had previously observed that the epicardial mouse AP, exhibits a phase 2 that is reduced by ryanodine (Ry) and thapsigargin (Tg). To investigate if Im is directly activated by the SR Ca2+ release during the phase 2, nifedipine photolysis was used. We found a late-inward current (Ilate) that was abolished by Ry and Tg. To determine if the NCX was responsible for Ilate, the NCX blocker SEA0400 was used. SEA0400 had a similar effect on AP phase 2 as that observed with Ry and Tg. To further test if the SEA0400 effect was the result of impairing the Ca2+ removal, intracellular Ca2+ transients were studied. Consistent with NCX blockade, SEA0400 increased the amplitude of the Ca2+ transients. In addition, to determine if NCX current can be activated during diastole, intracellular NP-EGTA was photolyzed to activate a Ca2+ dependent conductance. Our results revealed a diastolic inward current that increased with the photolysis extent and that was partially blocked by SEA0400. Our data demonstrate that during an epicardial AP there is a late influx of Na+ mediated by Ca2+ activation of NCX and that this exchanger, can also be activated by Ca2+ during diastole. This finding is relevant because the Ca2+ activation of this transporter is likely to be involved in the genesis of pro-arrhythmogenic conditions.
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