Control of cardiac sodium pump by long-chain acyl coenzymes A.
Since we had shown recently that fatty acyl-CoA derivatives stimulate (Na+ + K+)-ATPase activity at suboptimal ATP concentrations, we used sealed vesicles of beef heart sarcolemma to examine the effects of these compounds on the transport function of the enzyme. The sodium pump was detected in inside-out vesicles as a component of Na+ uptake that was dependent on intravesicular (extracellular) K+ and extravesicular (intracellular) ATP and was sensitive to vanadate and digitoxigenin. The pump flux was stimulated without a lag by palmitoyl-CoA (K0.5 = 3 microM) when ATP concentration was 50 microM, but not when it was 2 mM. Saturating palmitoyl-CoA reduced the K0.5 of ATP for the pump by a factor of 3-6. Raising the intracellular K+ concentration increased the K0.5 of ATP, and this effect of K+ was antagonized by palmitoyl-CoA. At concentrations up to 0.5 mM, palmitoyl-CoA had no effect on ATP-independent (passive) Na+ uptake. All tested long-chain acyl-CoA derivatives had effects similar to that of palmitoyl-CoA; but CoA, acetyl-CoA, and palmitic acid were ineffective. Palmitoyl carnitine and docosahexanoic acid, amphiphilic compounds with inhibitory and biphasic effects on the hydrolytic activity of purified (Na+ + K+)-ATPase, had purely inhibitory effects on the pump at high concentrations that also affected the passive fluxes. The data support the proposition that fatty acyl-CoA derivatives mimic the effect of ATP at a regulatory site and suggest that these intracellular liponucleotides may be involved in the control of the pump.
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004073:Digitoxigenin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology
D000214:Acyl Coenzyme A; D007473:Ion Channels; D014639:Vanadium; D004073:Digitoxigenin; D010171:Palmitoyl Coenzyme A; D014638:Vanadates; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium