Inhibition of CA2+Efflux by Pyridine Nucleotides

The effects of pyridine nucleotides on the Mg-dependent ATP-stimulated Ca2+ pump and on the ATP-independent Na(+)-Ca2+ exchanger were investigated in rat brain synaptic plasma membranes. Both Ca2+ efflux mechanisms are inhibited by pyridine nucleotides, in the order NADPH greater than NADP greater than NADH greater than NAD with IC50 = ca. 3-4 mM for NADP or NADPH and ca. 5 mM for the other pyridine nucleotides in the case of the ATP-driven Ca(2+)-pump, and with IC50 = 8 to 10 mM for the Na(+)-Ca2+ exchanger. Oxidizing agents such as DCIP or FeCN also affect the Ca(2+)-efflux mechanisms. DCIP and FeCN inhibit the ATP-driven Ca2+ pump but not the Na(+)-Ca2+ exchanger. Inhibition of the ATP-dependent Ca2+ pump is optimal when both a reduced pyridine nucleotide and an oxidizing agent (e.g. DCIP or FeCN) were added together. Under similar experimental conditions the pyridine nucleotide-mediated inhibition of the Na(+)-Ca2+ exchanger is partially removed. Therefore Ca(2+)-efflux mechanisms appear to be controlled in part through the redox environment, probably by means of transplasma membrane dehydrogenases.