Acute hyperglycemia induces Cardiac Mitochondrial Depolarization

Abstract

Mitochondrial ATP generation depends on the enormous potential across the inner mitochondrial membrane (ΔΨmito ~ −180 mV), among many other factors. Oxidative phosphorylation requires the large ΔΨmito 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 ΔΨmito under photonic stress in rat ventricular myocytes. Using tetra-methyl rhodamine methyl ester (TMRM) as a fluorescence monitor of ΔΨmito we examined how the time-dependent depolarization of mitochondria may be altered by hyperglycemia. Using a normal Tyrode's solution on isolated ventricular myocytes, changing the [glucose] has dramatic effect on the rate of ΔΨmito depolarization. After 3hours of hyperglycemic exposure, the rate of depolarization is reduced nearly 30% compared to controls. Antioxidant treatment protects cardiac myocytes from this hyperglycemic-induced effect while selectively inhibiting complex I causes an abrogation of the effect. These data elucidate the biophysical effects of acute hyperglycemia on cardiac myocytes.