Relative roles of intracellular Ca2+ and pH in shaping myocardial contractile response to acute respiratory alkalosis

H. Kusuoka, P. H. Backx, M. C. Camilion de Hurtado, M. Azan-Backx, E. Marban, H. E. Cingolani

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During acute respiratory alkalosis, myocardial contractility initially increases but then declines toward control levels. To elucidate the mechanism of this response, two parallel strategies were adopted: isovolumic left ventricular developed pressure (DP) and intracellular pH (pH(i)) were measured in isolated ferret hearts using 31P-nuclear magnetic-resonance spectroscopy, and isometric developed tension (DT) and intracellular Ca2+ concentration ([Ca2+](i)) were measured in ferret papillary muscles using microinjected fura 2 salt. When hypocapnia was induced by sudden introduction of perfusate equilibrated with 2% CO2 (from 5% CO2 in control), DP increased to a maximum of 120 ± 3% (SE; n = 7) of control within 40 s. Afterward, DP decreased toward control levels, reaching a new steady state in 2-3 min. In contrast, pH(i) increased from control (7.11 ± 0.01) only after 30 s of hypocapnia and reached a peak of 7.25 ± 0.02 between 80 and 100 s. Thus pH(i) lagged behind contractility. In contrast to pH(i), [Ca2+](i) changed in parallel with DT; when DT reached a maximum (251 ± 63% of control; n = 5) during hypocapnia, the amplitude of [Ca2+](i) transients also peaked (190 ± 22% of control; n = 5). A simulation of contractile force based on our measurements of pH(i) and [Ca2+](i) along with published Ca2+-tension relations, described adequately the changes in developed force during hypocapnia. These results indicate that the biphasic changes in [Ca2+](i), coupled with an out-of-phase change in pH(i), underlie the biphasic response of myocardial contractility to hypocapnia.

Original languageEnglish (US)
Pages (from-to)H1696-H1703
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5 34-5
StatePublished - 1993


  • hypocapnia
  • intracellular calcium concentration
  • intracellular pH

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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