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 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.

In vivo creatine kinase reaction kinetics at rest and stress in type II diabetic rat heart

“…In particular, the spontaneous heart rate reported in diabetic heart was about 30% lower and the rate pressure product (RPP) was about half that found in control hearts (Jilkina et al. ; Miki et al. ).…”

Changes in mitochondrial morphology and organization can enhance energy supply from mitochondrial oxidative phosphorylation in diabetic cardiomyopathy

“…diabetic cardiomyopathy; oxidative phosphorylation; mitochondrion dynamics; cardiac ultrastructure DIABETIC CARDIOMYOPATHY is in part induced by metabolic dysfunction within cardiac mitochondria. It is characterized by metabolic alterations such as an overdependence on fatty acid oxidation (6) and subsequent mitochondrial inefficiencies (26) characterized by increased reactive oxidative species (ROS) production (21,24) and decreased ATP and phosphocreatine (PCr) concentrations (17). These metabolic alterations coincide with changes to the subcellular ultrastructure, such as increased lipid and glycogen deposition, loss of myofibrils, and changes to mitochondrial morphology and arrangement within the cell (2,3,8,11).…”

Effects of altered cellular ultrastructure on energy metabolism in diabetic cardiomyopathy – an in-silico study

“…T1D cardiomyopathy is one of the T1D induced disease processes, commonly associated with left ventricular diastolic dysfunction with normal ejection fraction (3). It exhibits many common metabolic conditions accompanying heart failure, e.g., increased synthesis of reactive oxygen species (ROS) (4,5), impaired mitochondrial oxidative phosphorylation (OXPHOS) (5)(6)(7) and decrease in both cellular reserve of phosphocreatine (PCr) and activity of mitochondrial creatine kinase (mtCK) enzymes regulating PCr levels (8,9). T1D cardiomyopathy is also accompanied by alterations in the ultrastructure of cardiomyocytes.…”