Increased Exchange Current but Normal Ca 2+ Transport via Na + -Ca 2+ Exchange During Cardiac Hypertrophy After Myocardial Infarction

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Abstract
Hypertrophied and failing cardiac myocytes generally show alterations in intracellular Ca 2+ handling associated with changes in the contractile function and arrhythmogenicity. The cardiac Na + -Ca 2+ exchange (NCX) is an important mechanism for Ca 2+ extrusion and cell relaxation. Its possible involvement in changes of excitation-contraction coupling (EC-coupling) with disease remains uncertain. We analyzed the NCX function in rat ventricular myocytes 5 to 6 months after experimental myocardial infarction (PMI) produced by left coronary artery ligation and from sham-operated (SO) hearts. Caged Ca 2+ was dialyzed into the cytoplasm via a patch-clamp pipette and Ca 2+ was released by flash photolysis to activate NCX and measure the associated currents ( I NaCa ), whereas [Ca 2+ ] i changes were simultaneously recorded with a confocal microscope. I NaCa density normalized to the [Ca 2+ ] i jumps was 2.6-fold higher in myocytes from PMI rats. The level of total NCX protein expression in PMI myocytes was also increased. Interestingly, although the I NaCa density in PMI cells was larger, PMI and SO myocytes presented virtually identical Ca 2+ transport via the NCX. This discrepancy was explained by a reduced surface/volume ratio (34.8%) observed in PMI cells. We conclude that the increase in NCX density may be a mechanism to maintain the required Ca 2+ extrusion from a larger cell to allow adequate relaxation.