'Calcium paradox' in the heart is modulated by cell sodium during the calcium-free period

Gualberto Ruaño-Arroyo, Gary Gerstenblith, Edward G. Lakatta

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32 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)783-793
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Issue number9
StatePublished - Sep 1984


  • 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


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