DOES ATP DEPLETION INHIBIT PLASMA MEMBRANE Ca2+-ATPase ACTIVITY DURING METABOLIC INHIBITION?
The answer to this question will depend on the “extent” of metabolic stress and whether mitochondria or glycolysis is inhibited. It will also depend on the method of choice for measuring ATP depletion, how quickly ATP is depleted and whether this is sufficient to inhibit the PMCA. We have previously reported that oxidative stress, induced by H2O2, which is known to inhibit both mitochondrial and glycolytic metabolism[34], induced an irreversible Ca2+ overload and marked inhibition of the PMCA in pancreatic acinar cells[31,35]. This H2O2-induced PMCA inhibition could occur without mitochondrial Ca2+ handling, coincided with mitochondrial depolarization and was sensitive to inhibitors of the mitochondrial permeability transition pore (mPTP)[31]. However, based on our MgGreen measurements of ATP, inhibition of the PMCA could occur independent or prior to any substantial ATP depletion.
