Control of cardiac sarcolemmal adenylate cyclase and sodium, potassium-activated adenosinetriphosphatase activities.
A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase activity of 4-6 mu moles P1/hour mg-1 protein, measured in 120 mM NaC1 or KC1, was approximately doubled in 100 mM NaC1 plus 20 mM KC1. This increment, the Na, K-ATPase, was abolished by 10-5M ouabain, the K1 for ouabain being approximately 3 X 10-7M. 1-Epinephrine had no effect on Na, K-ATPase, but NaF was inhibitory. Adenylate cyclase, which had a basal activity of approximately 50% by NaC1 or KC1 alone at concentrations up to 0.2M. There was no additional stimulation of adenylate cyclase activity when na+ K+ included together. Both 1-epinephrine and NaF cause significant stimulation of adenylate cyclase, but neither basal nor activated cyclic AMP PRODUCTION WAS INFLUENCED BY OUABAIN. Half-maximal stimulation was seen at approximately 5 X 10-6M 1-epinephrine. Both the catecholamine and NaF increased the V-max ofcardiac plasma membrane adenylate cyclase without significantly influencing Km. Increasing Ca2+ in the range between 10-7 and 10-3M inhibited basal, 1-epinephrine-stimulated, and NaF-stimulated activities. Basal rates of cyclic AMP production were more sensitive to Ca2+ than was 1-epinephrine stimulation was increased from approximately 60% in 0.5 mM EGTA to approximately 150% in 10-7M Ca2+ and 400% in 10-5M Ca2+. The inhibitory effect of Ca2+ on adenylate cyclase activity may represent a negative feed back mechanism by which elevation of intracellular Ca2+ concentration lowers cellular levels of cyclic AMP and thus reduces Ca2+ influx into the myocardium.
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D009206:Myocardium / Q000201:enzymology*; D011188:Potassium; D012508:Sarcolemma / Q000187:drug effects / Q000201:enzymology*; D012964:Sodium
D012964:Sodium; D000251:Adenosine Triphosphatases; D000262:Adenylyl Cyclases; D011188:Potassium; D002118:Calcium; D004837:Epinephrine