title: Regulation of canine heart sarcolemmal Ca2+-pumping ATPase by cyclic GMP.
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 Ca2+-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 Mg2+-dependent 45Ca2+ 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 (Ca2+ + Mg2+)-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 45Ca2+ uptake was associated with a significant decrease in the pump Vmax, and at the most effective concentration of cyclic GMP increased the apparent Km for Ca2+. These results suggest that cyclic GMP may depress ventricular Ca2+ efflux by decreasing the enzyme turnover and to a limited extent, decreasing pump affinity for Ca2+. 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 Ca2+.
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D006152:Cyclic GMP / Q000494:pharmacology*; D004285:Dogs; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D008274:Magnesium; D002118:Calcium