Halothane alters cytosolic calcium transient in tracheal smooth muscle.
Halothane is a potent bronchodilator that attenuates vagally mediated constriction of canine airways, in part by a direct action on the smooth muscle cell. In tracheal smooth muscle, acetylcholine (ACh) produces a transient peak increase in cytosolic ionized calcium concentration ([Ca2+]i), which declines to a sustained plateau concentration that is higher than that of the unstimulated muscle, and a sustained increase in force. The transient peak [Ca2+]i is caused primarily by Ca2+ release from the sarcoplasmic reticulum (SR), whereas the plateau [Ca2+]i is caused primarily by influx of extracellular Ca2+ across the plasma membrane. This study was conducted to investigate the effects of halothane on the 1) transient peak [Ca2+]i during force development (i.e., developed force) and 2) plateau [Ca2+]i during force maintenance (i.e., sustained force) induced by ACh in isolated strips of canine tracheal smooth muscle. Changes in [Ca2+]i were measured with the photoprotein, aequorin. In muscle strips contracted after incubation with 1.1 (n = 5) or 1.5 (n = 5) minimum alveolar concentration (MAC) halothane, halothane significantly attenuated the transient peak aequorin luminescence (AL) and developed force and significantly prolonged the time necessary to reach peak AL and developed force; these effects were not dose dependent. In muscle strips (n = 3) contracted with ACh, addition of halothane caused a reduction in sustained force but no decrease in plateau AL.(ABSTRACT TRUNCATED AT 250 WORDS)
Jones
K A
KA
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.
Housmans
P R
PR
Warner
D O
DO
Lorenz
R R
RR
Rehder
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000331:Aequorin / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism*; D004285:Dogs; D004594:Electrophysiology; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D000331:Aequorin; D000109:Acetylcholine; D002118:Calcium; D006221:Halothane