British Journal of Anaesthesia, Vol 76, Issue 6 847-853, Copyright © 1996 by The Board of Management and Trustees of the British Journal of Anaesthesia
T. Fukushima, A. Hirasaki, K. A. Jones and D. O. Warner
Earlier studies have suggested that halothane may relax smooth muscle in
part by opening adenosine triphosphate-sensitive potassium (KATP) channels.
We tested this hypothesis in vitro by examining the interaction of
halothane with glibenclamide, a KATP channel blocker, and YM934, a KATP
channel opener, in strips of canine tracheal smooth muscles mounted in an
organ bath system. To examine the specificity of any effects of halothane
on the KATP channel, we assessed the interaction of halothane with
tetraethylammonium (TEA), an antagonist of the large-conductance,
calcium-activated potassium channel. Experiments were conducted with drugs
added before exposure to increasing concentrations of acetylcholine (ACh),
and with drugs added after stable increases in force produced by ACh were
achieved (ACh precontraction). Exposure to halothane 0.62 mmol litre-1
(equivalent to approximately 2 MAC) increased significantly the ED50 for
ACh-induced contractions (by 0.24 (SEM 0.07) mumol litre-1). TEA 1 mmol
litre-1 but not glibenclamide 10 mumol litre-1 significantly augmented this
increase in ED50 (by an additional 0.17 (0.06) mumol litre-1). In strips
precontracted with ACh, TEA, but not glibenclamide, potentiated
concentration-dependent relaxation induced by halothane. Incubation with
YM934 0.32 mumol litre-1 increased significantly the ED50 for ACh- induced
contractions (from 0.12 (0.02) to 0.55 (0.11) mumol litre-1), an increase
not affected by exposure to halothane 0.72 mmol litre-1. When added to
strips precontracted with approximately ACh 0.3 mumol litre-1, YM934
produced concentration-dependent relaxation; halothane had little effect on
this relaxation. These results do not support the hypothesis that halothane
relaxes canine tracheal smooth muscle in part by opening KATP channels.
LABORATORY INVESTIGATIONS
Halothane and potassium channels in airway smooth muscle
Departments of Anesthesiology and of Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA
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