Mechanism of the ATP-induced rise in cytosolic Ca2+ in freshly isolated smooth muscle cells from human saphenous vein.
Effects of exogenous adenosine 5'-triphosphate (ATP) were studied by measurements of intracellular Ca2+ concentration ([Ca2+]i) and membrane currents in myocytes freshly isolated from the human saphenous vein. At a holding potential of -60 mV, ATP (10 microM) elicited a transient inward current and increased [Ca2+]i. These effects of ATP were inhibited by alpha,beta-methylene adenosine 5'-triphosphate (AMP-CPP, 10 microM). The ATP-gated current corresponded to a non-selective cation conductance allowing Ca2+ entry. The ATP-induced [Ca2+]i rise was abolished in Ca(2+)-free solution and was reduced to 30.1 +/- 5.5% (n = 14) of the control response when ATP was applied immediately after caffeine, and to 23.7 +/- 3.8% (n = 11) in the presence of thapsigargin. The Ca(2+)-induced Ca2+ release blocker tetracaine inhibited the rise in [Ca2+]i induced by both caffeine and ATP, with apparent inhibitory constants of 70 microM and 100 microM, respectively. Of the ATP-induced increase in [Ca2+]i 29.3 +/- 3.9% (n = 8) was tetracaine resistant. It is concluded that the effects of ATP in human saphenous vein myocytes are only mediated by activation of P2x receptor channels. The ATP-induced [Ca2+]i rise is due to both Ca2+ entry and Ca2+ release activated by Ca2+ ions that enter the cell through P2x receptor channels.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000368:Aged; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005343:Fibrinolytic Agents; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012501:Saphenous Vein / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D013729:Terpenes; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D006493:Heparin; D000252:Calcium-Transporting ATPases; D002118:Calcium