Metabolic inhibition in the perfused rat heart: evidence for glycolytic requirement for normal sodium homeostasis.

Abstract

Subcellular compartmentalization of energy stores to support different myocardial processes has been exemplified by the glycolytic control of the ATP-sensitive K+ channel. Recent data suggest that the control of intracellular sodium (Nai) may also rely on glycolytically derived ATP; however, the degree of this dependence is unclear. To examine this question, isolated, perfused rat hearts were exposed to hypoxia, to selectively inhibit oxidative metabolism, or iodoacetate (IAA, 100 mumol/l), to selectively inhibit glycolysis. Nai and myocardial high-energy phosphate levels were monitored using triple-quantum-filtered (TQF) 23Na and 31P magnetic resonance spectroscopy, respectively. The effects of ion exchange mechanisms (Na+/Ca2+, Na+/H+) on Nai were examined by pharmacological manipulation of these channels. Nai, as monitored by shift reagent-aided TQF 23Na spectral amplitudes, increased by approximately 220% relative to baseline after 45 min of perfusion with IAA, with or without rapid pacing. During hypoxia, Nai increased by approximately 200% during rapid pacing but did not increase in unpaced hearts or when the Na+/H+ exchange blocker ethylisopropylamiloride (EIPA, 10 mumol/l) was used. Neither EIPA nor a low-Ca2+ perfusate (50 mumol/l) could prevent the rise in Nai during perfusion with IAA. Myocardial function and high-energy phosphate stores were preserved during inhibition of glycolysis with IAA and continued oxidative metabolism. These results suggest that glycolysis is required for normal Na+ homeostasis in the perfused rat heart, possibly because of preferential fueling of Na-K-adenosinetriphosphatase by glycolytically derived ATP.

• Authors: J Dizon, D Burkhoff, J Tauskela, J Whang, P Cannon, J Katz
• Journal: The American journal of physiology (Am J Physiol) Vol. 274 Issue 4 Pg. H1082-9 (04 1998) ISSN: 0002-9513 [Print] United States
• PMID: 9575910 (Publication Type: Journal Article)

Chemical References

• Iodoacetates
• Phosphates
• Sodium-Hydrogen Exchangers
• Sodium
• Calcium
• Iodoacetic Acid

Topics

• Animals
• Calcium (metabolism)
• Cardiac Pacing, Artificial
• Energy Metabolism (physiology)
• Glycolysis (drug effects, physiology)
• Homeostasis (physiology)
• Hypoxia (metabolism)
• In Vitro Techniques
• Iodoacetates (pharmacology)
• Iodoacetic Acid
• Magnetic Resonance Spectroscopy (methods)
• Male
• Myocardium (metabolism)
• Perfusion
• Phosphates (metabolism)
• Rats
• Rats, Wistar
• Reference Values
• Sodium (metabolism)
• Sodium-Hydrogen Exchangers (physiology)