Potassium fluxes, energy metabolism, and oxygenation in intact diabetic rat hearts under normal and stress conditions

Abstract

We evaluated the function of Na+/K+ATPase and sarcolemmal KATPchannels in diabetic rat hearts. Six weeks after streptozotocin (STZ) injection, unidirectional K+fluxes were assayed by using87rubidium (87Rb+) 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. KATP-mediated Rb+efflux was activated metabolically with 2,4-dinitrophenol (DNP, 50 µmol·L–1) or pharmacologically with a KATPchannel opener, P-1075 (5 µmol·L–1). Cardiac energetics were monitored by using31P 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 KATPchannel; 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 KATPchannel 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.