Na-H exchange in myocardium: Effects of hypoxia and acidification on Na and Ca

S. E. Anderson, E. Murphy, C. Steenbergen, R. E. London, Peter M Cala

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145 Scopus citations

Abstract

Historically, increases in cell Na content during ischemic and hypoxic episodes were thought to result from impaired ATP production causing decreased Na+-K+ATPase activity. Here we report the results of testing the alternate hypothesis that hypoxia-induced Na uptake is 1) the result of increased entry, as opposed to decreased extrusion 2) via Na-H exchange operating in a pH regulatory capacity and that cell Ca accumulation occurs via Na-Ca exchange secondary to collapse of the Na gradient. We used 23Na-, 19F-, and 31P-nuclear magnetic resonance (NMR) to measure intracellular Na content (Na(i)), Ca concentration ([Ca](i)), pH (pH(i)), and high-energy phosphates in Langendorff-perfused rabbit hearts. When the Na+-K+-ATPase was inhibited by ouabain and/or K-free perfusion, hearts subjected to hypoxia gained Na at a rate >10 times that of normoxic controls [during the first 12.5 min Na(i) increased from 7.9 ± 5.8 to 34.9 ± 11.0 (SD) meq/kg dry wt compared with 11.1 ± 16.3 to 13.6 ± 9.0 meq/kg dry wt, respectively]. When normoxic hearts were acidified using a 20 mM NH4Cl prepulse technique, pH(i) rapidly fell from 7.27 ± 0.24 to 6.63 ± 0.12 but returned to 7.07 ± 0.10 within 20 min, while Na uptake was similar in rate and magnitude to that observed during hypoxia (24.5 ± 13.4 to 132.1 ± 17.7 meq/kg dry wt). During hypoxia and after NH4Cl washout, increases in [Ca](i) were similar in time course to those observed for Na(i). Increases in Na(i) were insensitive to benzamil (50μM) and bumetanide (10 μM), whereas increases in Na(i) as well as pH(i)regulation (after NH4Cl washout) and increases in [Ca](i) were inhibited by amiloride (1 mM) and 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 100 μM). EIPA and amiloride also decreased changes in coronary resistance and phosphocreatine measured after 60 min of hypoxic perfusion (P < 0.05). These results are consistent with our hypothesis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume259
Issue number6 28-6
StatePublished - 1990

Keywords

  • adenosinetriphosphatase
  • amiloride
  • Langendorff- perfused rabbit hearts
  • sodium-potassium

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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