Glycolysis is necessary to preserve myocardial Ca2+ homeostasis during β-adrenergic stimulation

K. Nakamura, H. Kusuoka, G. Ambrosio, L. C. Becker

Research output: Contribution to journalArticle

Abstract

Although ATP derived from glycolysis represents only a small fraction of total myocardial ATP production, metabolic compartmentation may result in preferential use of glycolytic ATP for certain membrane activities, including pumping of Ca2+ from the cytoplasm. We tested this hypothesis by looking for evidence of Ca2+ overload in normoxic perfused rabbit hearts given iodoacetate (IAA, 50 μM) to block glycolysis and isoproterenol (Iso, 0.05 μM) to stimulate Ca2+ entry. The hearts beat isovolumically and were perfused with 16 mM glucose and 5 or 10 mM pyruvate (to preserve oxidative metabolism) in a superconducting magnet for 31P-nuclear magnetic resonance (NMR) measurements of high energy phosphates or 19F-NMR measurements of intracellular free Ca2+ concentration ([Ca2+](i)). IAA by itself had no effect on left ventricular (LV) developed pressure, end-diastolic pressure, pressure-rate product, or tissue high-energy phosphates. During exposure to Iso, mean LV end-diastolic pressure increased from 10.7 to 49.3 mmHg in hearts pretreated with IAA (n = 7) but did not change in control hearts (n = 7). During Iso, there were substantial reductions in developed pressure, ATP, and phosphocreatine in IAA-treated hearts but not in control hearts. After exposure to IAA and Iso, a doubling of diastolic [Ca2+](i) was observed with 19F-NMR. In IAA-treated hearts, reduction of perfusate Ca2+ concentration from 2.5 to 0.6 mM during Iso exposure (n = 6) prevented the mechanical dysfunction and decrease in high-energy phosphates. These findings suggest that glycolysis is necessary to preserve myocardial Ca2+ homeostasis during β-adrenergic stimulation.

Original languageEnglish (US)
Pages (from-to)H670-H678
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number3 33-3
StatePublished - Jan 1 1993

Keywords

  • calcium ion
  • heart
  • iodoacetate
  • isoproterenol

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Glycolysis is necessary to preserve myocardial Ca<sup>2+</sup> homeostasis during β-adrenergic stimulation'. Together they form a unique fingerprint.

  • Cite this