Adenine nucleotides stimulate oxidation-induced calcium efflux from sarcoplasmic reticulum vesicles

Micromolar concentrations of copper (Cu2+) and cysteine induce rapid efflux of calcium from sarcoplasmic reticulum (SR) vesicles. This effect appears to be due to a Cu2+-catalyzed oxidation of the added cysteine to a critical sulfhydryl group on the release protein from sarcoplasmic reticulum (J. L. Trimm, G. Salama, and J. J. Abramson (1986) J. Biol. Chem. 261, 16092-16098). The data presented here indicate that adenine nucleotides synergistically stimulate copper/cysteine (oxidation)-induced calcium efflux from SR vesicles. The order of effectiveness in stimulating calcium efflux is ATP greater than AMP-PCP greater than cAMP greater than AMP greater than adenine approximately NAD approximately NADH. Non-adenine-containing nucleotides such as GTP, CTP, UTP, and ITP and the high energy phosphate compound, acetyl phosphate, were ineffective in stimulating oxidation-induced calcium efflux. The relative effectiveness of various adenine nucleotides in stimulating calcium-induced calcium efflux and oxidation-induced calcium efflux are identical, suggesting that a common mode of action is involved when calcium release is triggered by either method. The stimulatory effect of the adenine nucleotides on oxidation-induced efflux is independent of external magnesium concentration and independent of the magnesium gradient across the SR membrane.