Halothane reduces myofilament ca2+ sensitivity during muscarinic
receptor stimulation of airway smooth muscle.
Akao, Masaki, Akihito Hirasaki, Keith A. Jones, Gilbert Y. Wong,
Dorothee H. Bremerich, David O. Warner.
Departments of Anesthesiology, and Physiology and Biophysics, Mayo
Clinic and Mayo Foundation, Rochester, MN
APStracts 3:0111L, 1996.
This study used a [beta]-escin-permeabilized canine tracheal smooth
muscle (CTSM) preparation to test the hypothesis that the volatile
anesthetic halothane decreases myofilament calcium (Ca2+) sensitivity
by inhibiting the membrane receptor-linked second messenger systems
that regulate myofilament Ca2+ sensitivity and not by inhibiting
Ca2+-calmodulin activation of the contractile proteins. Acetylcholine
(ACh) caused a GTP-dependent increase in force at constant submaximal
cytosolic Ca2+ concentration ([Ca2+]i). ACh, guanosine-5'-O-(3
-thiotriphosphate), and the protein kinase C agonist 12,13-phorbol
dibutyrate each significantly decreased the EC50 for free Ca2+ from
0.77+/-0.09 [mu]M (Ca2+ alone) to 0.16+/-0.01, 0.19+/-0.02, and
0.37+/-0.03 [mu]M, respectively, demonstrating an increase in
myofilament Ca2+ sensitivity. Halothane (0.92+/-0.12 mM) had no
effect on the free Ca2+ concentration-response curves generated by
Ca2+ alone. However, in the presence of 0.3 [mu]M ACh plus 10 [mu]M
GTP to maximally activate muscarinic receptors, halothane
significantly increased the EC50 for free Ca2+ from 0.17+/-0.01 [mu]M
to 0.38+/-0.03 [mu]M. These findings suggest that halothane decreases
myofilament Ca2+ sensitivity in [beta]-escin-permeabilized CTSM by
inhibiting the membrane receptor-linked second messenger systems that
regulate myofilament Ca2+ sensitivity.
Received 20 February 1996; accepted in final form 13 June 1996.
APS Manuscript Number L51-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996