Potassium fluxes, energy metabolism, and oxygenation in intact diabetic rat hearts under normal and stress conditions.
We evaluated the function of Na(+)/K(+) ATPase and sarcolemmal K(ATP) channels in diabetic rat hearts. Six weeks after streptozotocin (STZ) injection, unidirectional K(+) fluxes were assayed by using (87)rubidium ((87)Rb(+)) MRS. The hearts were loaded with Rb(+) by perfusion with Krebs-Henseleit buffer, in which 50% of K(+) was substituted with Rb(+). The rate constant of Rb(+) uptake via Na(+)/K(+) ATPase was reduced. K(ATP)-mediated Rb(+) efflux was activated metabolically with 2,4-dinitrophenol (DNP, 50 micromol.L(-1)) or pharmacologically with a K(ATP) channel opener, P-1075 (5 micromol.L(-1)). Cardiac energetics were monitored by using (31)P MRS and optical spectroscopy. DNP produced a smaller ATP decrease, yet similar Rb(+) efflux activation in STZ hearts. In K(+)-arrested hearts, P-1075 had no effect on high-energy phosphates and stimulated Rb(+) efflux by interaction with SUR2A subunit of K(ATP) channel; this stimulation was greater in STZ hearts. In normokalemic hearts, P-1075 caused cardiac arrest and ATP decline, and the stimulation of Rb(+) efflux was lower in normokalemic STZ hearts arrested by P-1075. Thus, the Rb(+)efflux stimulation in STZ hearts was altered depending on the mode of K(ATP) channel activation: pharmacologic stimulation (P-1075) was enhanced, whereas metabolic stimulation (DNP) was reduced. Both the basal concentration of phosphocreatine ([PCr]) and [PCr]/[ATP] were reduced; nevertheless, the STZ hearts were more or equally resistant to metabolic stress.
Institute for Biodiagnostics, National Research Council of Canada, 435 Ellice Avenue, Winnipeg, MB R3B1Y6, Canada. olga.jilkina@nrc-cnrc.gc.ca
Olga
O
Jilkina
Bozena
B
Kuzio
Valery V
VV
Kupriyanov
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000465:Algorithms; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004734:Energy Metabolism / Q000502:physiology*; D006146:Guanidines / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D010759:Phosphorus Isotopes / Q000737:chemistry; D011188:Potassium / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D006146:Guanidines; D054086:KATP Channels; D010759:Phosphorus Isotopes; D011725:Pyridines; D012414:Rubidium Radioisotopes; C073896:N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D019297:2,4-Dinitrophenol; D011188:Potassium