Glucose Provides Short-Term Protection to Mitochondria in Rat Ventricular Cardiac Myocytes

Abstract

Cellular ATP production depends on glycolytic and oxidative phosphorylation pathways and hence on both cytosolic and mitochondrial reactions. Mitochondrial ATP generation depends on the enormous potential across the inner mitochondrial membrane (αΨmito ∼ −180 mV), among many other factors. Using tetra-methyl rhodamine methyl ester (TMRM) as a fluorescence monitor of αΨmito we examined how the time-dependent and illumination-dependent depolarization of mitochondria may be altered by extracellular glucose. Oxidative phosphorylation requires the large αΨmito and when the mitochondria are depolarized, oxidative phosphorylation becomes uncoupled and ATP production falls. Here we investigate the effect of hyperglycemia (30 mM versus the physiological glucose of 5 mM) on mitochondrial αΨmito under photon-induced oxidative stress in rat ventricular myocytes. Using a buffered physiologic salt solution on quiescent ventricular myocytes, changing the [glucose] has dramatic effect on the rate of αΨmito depolarization. The rate of depolarization was significantly decreased in the presence of high glucose (the time-to-50% depolarization was increased from 250 s to 500s). These results were carried out in the absence of insulin. We conclude that hyperglycemia appears to protect mitochondrial function in quiescent heart cells from photon-induced oxidative stress. It is not yet clear how this apparent protection may change as metabolic load and muscle work increases, nor is it clear whether the absence of fatty acid substrates will increase or decrease this seemingly protective effect.