title: Calcium regulation of glycolysis, glucose oxidation, and fatty acid oxidation in the aerobic and ischemic heart.
abstract: Although Ca2+ is an important regulator of energy metabolism, the effects of increasing extracellular [Ca2+] on energy substrate preference are not clear. We determined the relationship between [Ca2+], fatty acids, and ischemia on rates of glycolysis, glucose oxidation, and palmitate oxidation in isolated working rat hearts. Hearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose, 100 microU/mL insulin, and either 1.25 or 2.5 mM Ca2+, in the presence or absence of 1.2 mM palmitate. Rates of glycolysis and glucose oxidation or palmitate oxidation were measured in the hearts using [5-3H,14C(U)]glucose or [1-14C]palmitate, respectively. In the absence of fatty acids, glycolysis and glucose oxidation rates were similar, regardless of whether [Ca2+ was 1.25 or 2.5 mM. Addition of 1.2 mM palmitate to the perfusate of hearts perfused with 1.25 mM Ca2+ significantly decreased rates of both glycolysis (from 4623 +/- 438 to 1378 +/- 238 nmol.min-1.g-1 dry weight) and glucose oxidation (from 1392 +/- 219 to 114 +/- 22 nmol.min-1.g-1 dry weight). When [Ca2+] was increased from 1.25 to 2.5 mM in hearts perfused with 1.2 mM palmitate, glycolysis and glucose oxidation increased by 164 and 271%, respectively, with no change in palmitate oxidation rates. Increasing [Ca2+] from 1.25 to 2.5 mM increased the contribution of glucose to ATP production from 9.3 to 18.7%. When hearts were subjected to low-flow ischemia (by reducing coronary flow to 0.5 mL.min-1) oxidative metabolism was essentially abolished. Under these conditions, glycolytic rates were not dependent on either [Ca2+] or the presence or absence of fatty acids. These results demonstrate that perfusate [Ca2+] is an important determinant of myocardial glucose metabolism in aerobic hearts, and that glycolysis and glucose oxidation are more responsive to changes in [Ca2+] than is fatty acid oxidation.
authors.affiliation: Department of Pharmacology, University of Alberta, Edmonton, Canada.
authors.forename: B O
authors.initials: BO
authors.lastname: Schönekess
authors.forename: P G
authors.initials: PG
authors.lastname: Brindley
authors.forename: G D
authors.initials: GD
authors.lastname: Lopaschuk
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000332:Aerobiosis; D000818:Animals; D002118:Calcium / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010169:Palmitic Acids / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005227:Fatty Acids; D010169:Palmitic Acids; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose; D002118:Calcium