Wortmannin inhibits contraction without altering electrical
activity in canine gastric smooth muscle.
Burke, Edmund P., William T. Gerthoffer, Kenton M. Sanders & Nelson
G. Publicover.
Departments of Physiology and Pharmacology, University of Nevada
School of Medicine, MS 352, Reno, Nevada 89557-0046 USA, Phone: (702)
784-4952, FAX: (702) 784-6903, E-mail: nelson@unr.edu
APStracts 2:0442C, 1995.
Wortmannin, an inhibitor of myosin light chain kinase (10-30 [mu]M),
completely and irreversibly abolished (in 75% of tissues from canine
gastric antrum) phasic contractions caused by slow waves with no
significant effects on resting membrane potential or the frequency,
amplitude or duration of spontaneous slow waves. Responses to agents
that normally cause hyperpolarization (cromakalim, Na+ nitro-prusside
and forskolin) were unaffected by wortmannin treatment. It was also
possible to study the excitatory effects of agents and conditions
that normally result in loss of intracellular impalements: i)
elevated [K+]o altered membrane potential close to values predicted
by the Nernst equation and ii) high concentrations of acetylcholine
produced depolarization and rapid oscillations in membrane potential
coincident with contractile activity. Cholinergic increases in myosin
light chain phosphorylation and contractions were partially blocked
by wortmannin. In canine antrum, wortmannin inhibition of contraction
was irreversible, although in other tissue-types partial recovery of
contractions was observed when wortmannin was removed. Wortmannin can
be a useful agent to investigate the electrophysiology of some smooth
muscles when movement might lead to recording artifacts or loss of
signal.
Received 18 September 1995; accepted in final form 29 November
1995.
APS Manuscript Number C558-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95