Acetylcholine-induced chloride current oscillations in swine tracheal smooth muscle cells.
The activation of muscarinic receptors by acetylcholine (ACh) in tracheal smooth muscle cells induced Ca++ oscillations, measured as the activation of Ca(++)-dependent Cl- currents (Clca) at the K+ equilibrium potential. The currents were not abolished by replacement of external and internal K+ with Cs+ but decreased after reduction in internal Cl- concentration or extracellular application of niflumic acid, a Cl- channel blocker. The Clca oscillations were dependent on external Ca++ concentration ([Ca++]e). The mean current and frequency increased with increasing [Ca++]e, were enhanced by Bay K 8644 and were inhibited by verapamil, suggesting a role for voltage-operated Ca++ channels (VOC). Steady-state increases in Clca induced by 10(-6) M ACh could be converted to oscillations by reducing [Ca++]e or by buffering intracellular Ca++ with ethyleneglycolbis-N,N,N'-N'-tetraacetic acid (EGTA). Oscillations in Clca induced by 3 x 10(-8) and 10(-7) M ACh were more sensitive to EGTA than those induced by 10(-6) M ACh. Caffeine induced nonoscillatory, transient increases in Clca and reduced subsequent ACh-induced increases in Clca. The oscillatory patterns of Clca induced by ACh and the effects of modification of Ca++ influx were similar for oscillations in intracellular Ca++ concentration [Ca++]i as measured with confocal microfluorimetry. Thus, ACh-induced Clca oscillations reflect fluctuations in [Ca++]i that are consistent with initiation of Ca++ release from inositol-1,4,5-trisphosphate-(IP3)sensitive Ca++ stores. Maintenance of the oscillations requires Ca++ influx, in part through voltage-operated Ca++ channels.
Liu
X
X
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, USA.
Farley
J M
JM
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D003592:Cytophotometry; D003600:Cytosol / Q000378:metabolism; D004347:Drug Interactions; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D013552:Swine; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D015220:Calcium Channels; D018118:Chloride Channels; D002110:Caffeine; D000109:Acetylcholine; D002118:Calcium