Acetylcholine-induced chloride current oscillations in swine tracheal smooth muscle cells.

Xibao Liu,Jerry M. Farley

Published 1996 in Journal of Pharmacology and Experimental Therapeutics

ABSTRACT

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.

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