Blocking Mitochondrial Ca2+ Uptake Increases Matrix Reactive Oxygen Species During Excitation-contraction Coupling In Cardiac Myocytes

Abstract

Mitochondrial Ca2+ ([Ca2+]m) is taken up by the Ca2+-uniporter (mCU) and stimulates NADH- and ATP-production. Furthermore, the NADH redox state is in equilibrium with the NADPH- and glutathione-pools, and glutathione is required for glutathione peroxidase to eliminate H2O2. Thus, we hypothesized that inhibiting mitochondrial Ca2+-uptake could increase H2O2 formation. Experiments were performed in guinea-pig cardiac myocytes (n=10-13/group). To monitor [Ca2+]m, myocytes were loaded with rhod-2AM, and then patch-clamped and dialyzed with a pipette solution containing indo-1 to detect cytosolic [Ca2+] ([Ca2+]c).