Abstract
Cyclic nucleotide modulation of the sarcoplasmic reticulum calcium pump has been recognized for some time. Little is known, however, of cyclic nucleotide effects on the sarcolemmal Ca 2+ pump. In sarcolemmal vesicles prepared from ventricular muscle by a recent technique (Jones, L.R., Maddock, S.W. and Besch, H.R. (1980) J. Biol. Chem. 255, 9971–9980) we have demonstrated via Millipore filtration that 10 −8 M and 10 −9 M cyclic GMP depressed the rate of ATP- and Mg 2+-dependent 45Ca 2+ uptake by 34% and 52%, respectively. Only at millimolar levels did cyclic AMP have any effect and the respective 5′-nucleotides had no effect at all. Parallel measurement of the associated (Ca 2+ + Mg 2+)-ATPase in the presence of either cyclic or 5′-nucleotides, however, revealed no concomitant depression in ATP hydrolysis. In another series of experiments, the cyclic GMP effect on 45Ca 2+ uptake was associated with a significant decrease in the pump V max , and at the most effective concentration of cyclic GMP increased the apparent K m for Ca 2+. These results suggest that cyclic GMP may depress ventricular Ca 2+ efflux by decreasing the enzyme turnover and to a limited extent, decreasing pump affinity for Ca 2+. This supports a hypothesis whereby cyclic GMP might modulate both local biochemical and electrophysiological events by an effect on a discrete, regional pool of intracellular Ca 2+.
Published Version
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