We hypothesized that after a Ca2+-free period the magnitude of the Na+ gradient at the onset of Ca2+ reperfusion would grade the ensuing cell Ca2+ gain. Rabbit interventricular septa perfused with Hepes buffered solution (pH 7.4, [Ca2+]=1.0 mm) and stimulated to contract isometrically at 60 min-1 at 30°C were exposed to a 30-min Ca2+-free period followed by 30-min of Ca2+ re-introduction. Cell Na without Ca2+-free perfusion was 137±5 μmol/g dry wt. During the Ca2+-free period, the perfusate was manipulated to resultin three groups of septa in which cell Na just prior to Ca2+ re-introduction was 64±9 (perfusate [Na+ reduced to 47 mm), 170±12 (perfusate unaltered), and 293±16 μmol/g dry wt (addition of 5×10-5m ouabain). Following Ca2+ re-introduction, cell Ca2+ content was 3.4±0.5, 6.5±1.0, and 10.6±0.7 μmol/g dry wt in the low, intermediate, and high cell Na+ groups, respectively. Similar marked and highly significant gradations among the three groups were observed in the extent of cell K+ loss and recovery of contractile function during Ca2+ re-introduction. These results indicate that (1) myocardial cell Na+ increases during Ca2+ free perfusion and (2) the magnitude of the Na+ gradient at the end of the Ca2+ free period is an important determinant of the extent of cell Ca2+ gain, cell K+ loss, and reduction of contractile function with Ca2+ re-introduction, which collectively have been referred to as the 'calcium paradox' in the heart.
- Calcium paradox in the heart
- Calcium-induced cell death
- Na-dependent Ca influx
- Perfused rabbit interventricular septum
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine