The effects of halothane pretreatment on manganese influx induced by muscarinic stimulation of airway smooth muscle.
We hypothesized that halothane inhibits contraction of canine airway smooth muscle in part by depleting sarcoplasmic reticulum (SR) calcium stores, which affects subsequent force and calcium influx. This hypothesis was tested by using the rate of quenching of fura-2 fluorescence by manganese (Mn2+) as an index of calcium influx. When added 10 min before submaximum muscarinic stimulation (with 0.3 microM acetylcholine [ACh]), halothane (0.60 +/- 0.04 mM [mean +/- SE]) reduced subsequent isometric force and intracellular calcium concentration ([Ca2+]i) measured 10 min after contraction (to 55%) +/- 5% and 69% +/- 4% of control, respectively). The Mn2+ influx measured concurrently was significantly increased by halothane (by 57% +/- 22%). Depletion of SR calcium stores by ACh prior to contraction also increased Mn2+ influx (by 46% +/- 6%) but did not affect developed force or increase [Ca2+]i in response to submaximum muscarinic stimulation. Halothane did not affect [Ca2+]i or Mn2+ influx when added prior to maximum stimulation with 100 microM ACh but significantly reduced developed force. These findings are consistent with the hypothesis that halothane-induced SR depletion prior to contraction stimulates subsequent calcium influx, but they further suggest that halothane-induced SR depletion itself does not contribute significantly to the reduction in contractility produced by halothane in the canine airway smooth muscle.
Warner
D O
DO
Department of Anesthesiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. warner.david@mayo.edu
Jones
K A
KA
Lorenz
R R
RR
D000109:Acetylcholine / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D016257:Fura-2; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000378:metabolism / Q000493:pharmacokinetics*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013268:Stimulation, Chemical; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D018685:Anesthetics, Inhalation; D018678:Cholinergic Agents; D008345:Manganese; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2; D006221:Halothane