Regulation of [Ca2+]i in canine airway smooth muscle by Ca(2+)-ATPase and Na+/Ca2+ exchange mechanisms.
We investigated Ca2+ handling in airway smooth muscle (SM) using fura 2 fluorescence, ion currents, and contractions as indexes of intracellular Ca2+ concentration ([Ca2+]i). Carbachol evoked a transient elevation of [Ca2+]i, the magnitude of which was smaller and the rate of decay faster at 37 degrees C, indicating that some temperature-sensitive mechanism contributed to recovery. Removal of external Na+ had no effect on agonist-evoked Ca2+ transients or contractions or on spontaneous Ca(2+)-dependent K+ currents. Cyclopiazonic acid, a selective inhibitor of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, evoked a transient elevation of [Ca2+]i and contraction, markedly slowed recovery of the cholinergic Ca2+ transient, and depleted the SR. Sodium vanadate evoked a sustained elevation of [Ca2+]i and markedly slowed the decay of the cholinergic Ca2+ transient. We conclude that, in canine airway SM, 1) Na+/Ca2+ exchange makes at best only a minor contribution to Ca2+ homeostasis, 2) the SR Ca(2+)-ATPase compensates for spontaneous and agonist-triggered release of Ca2+, and 3) [Ca2+]i homeostasis involves some other extrusion pathway, likely the plasmalemmal Ca(2+)-ATPase.
Janssen
L J
LJ
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Walters
D K
DK
Wattie
J
J
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D018678:Cholinergic Agents / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009994:Osmolar Concentration; D011188:Potassium / Q000502:physiology; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D013696:Temperature; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014638:Vanadates / Q000494:pharmacology
D002352:Carrier Proteins; D018678:Cholinergic Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D019831:Sodium-Calcium Exchanger; D014638:Vanadates; D012964:Sodium; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid