title: 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.affiliation: Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dizon
authors.forename: D
authors.initials: D
authors.lastname: Burkhoff
authors.forename: J
authors.initials: J
authors.lastname: Tauskela
authors.forename: J
authors.initials: J
authors.lastname: Whang
authors.forename: P
authors.initials: P
authors.lastname: Cannon
authors.forename: J
authors.initials: J
authors.lastname: Katz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D004734:Energy Metabolism / Q000502:physiology; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
chemical_list: D007461:Iodoacetates; D010710:Phosphates; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D002118:Calcium; D019807:Iodoacetic Acid