Glutathione alters calcium responsiveness of cardiac skinned fibers

The glutathione status of cardiac muscle, that is the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) changes in certain forms of cardiomyopathy and during reperfusion of ischemic heart. Here we show that it also affects the sensitivity of contractile proteins to calcium. GSH (4 mM) increased the pCa50 for force development in skinned fibers by 0.2 pCa units and increased force by 44% +/- 5.4% at pCa 5.6 whereas GSSG (4 mM) decreased it by 54% +/- 17.8% at pCa 5.6. Half maximal activations and inhibitions were seen with 4 mM GSH or GSSG, respectively. In contrast to GSH, the reducing agent dithiothreitol at 5 mM had no activating effect. Our results suggest that the loss of contractility observed after a reperfusion of the ischemic heart may, at least in part, be due to a decreased responsiveness of the contractile proteins due to an altered glutathione status.