ATP activates K and Cl channels via purinoceptor-mediated release of Ca2+ in human coronary artery smooth muscle.
Coronary artery smooth muscle cells express G protein-coupled purinoceptors, and we report here for the first time how receptor activation by extracellular ATP influences cell membrane currents and membrane potential in human cells. ATP (100 microM) stimulated a triphasic change in membrane potential lasting several seconds, which was caused by sequential opening of transient inward and outward conductances. The inward current was carried by Cl- and the outward current by K+, as shown by ion substitution and changes in holding potential. Both currents were independent of the presence of external Ca2+ but were blocked by strong buffering of Ca2+ in the internal solution. The P2u- and P2y-purinoceptor agonists UTP and 2-methylthioadenosine 5'-triphosphate activated similar currents, whereas the P2x-receptor agonist alpha, beta-methyleneadenosine 5'-triphosphate and the P1-receptor agonist adenosine failed to stimulate any whole cell currents. The ATP-activated K+ current was inhibited by iberiotoxin (200 nM), and it was potentiated by the BK channel activator NS-1619 (30 microM). In cell-attached recordings, ATP activated a 230-pS BK channel. In conclusion, ATP acting via P2 purinoceptors stimulated release of Ca2+ from internal stores and transiently activated depolarizing Cl- and hyperpolarizing BK channels in human coronary artery smooth muscle cells.
Strøbaek
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NeuroSearch A/S, Smedeland, Glostrup, Denmark.
Christophersen
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Dissing
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Olesen
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D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014544:Uridine Triphosphate / Q000494:pharmacology
D018118:Chloride Channels; D007211:Indoles; D015221:Potassium Channels; D018048:Receptors, Purinergic P2; D013757:Tetraethylammonium Compounds; D013873:Thionucleotides; C048220:paxilline; D004533:Egtazic Acid; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate; C008501:2-methylthio-ATP