Signal transduction pathways causing slow synaptic excitation in
guinea-pig myenteric ah neurons.
Bertrand, P. P., and J. J. Galligan.
Department of Pharmacology and Toxicology, Michigan State
University, E. Lansing, MI 48824, USA
APStracts 2:0102G, 1995.
Intracellular recordings were obtained from myenteric AH neurons of
guinea-pig ileum in vitro. Slow excitatory synaptic responses
associated with decreased potassium conductance (gK), inhibition of
the spike afterhyperpolarization current (AHC) and increased chloride
conductance (gCl) were mimicked by senktide, a neurokinin-3 receptor
agonist. Intracellular GTP-_-S decreased gK and increased gCl
irreversibly after nerve stimulation or senktide application.
Myenteric neurons in pertussis toxin treated tissues responded
normally to senktide and nerve stimulation. Forskolin and phorbol
12,13 dibutyrate (PDBu) inhibited gK and the AHC, but did not
activate gCl. The AHC was not reduced by subthreshold concentrations
of forskolin (100 nM) or PDBu (3 nM) alone but was inhibited by
forskolin and PDBu applied together. Inhibitors of phospholipase C
(D609) or protein kinases (staurosporine) reduced slow synaptic and
senktide responses. The protein phosphatase inhibitor, calyculin A,
caused an inward current, a decrease in gK and AHC inhibition, but
did not activate gCl. We conclude that slow excitatory synaptic
responses are mediated by PTX-insensitive G-proteins and activation
of PLC and protein kinases. Forskolin and PDBu activate pathways that
inhibit gK. The mechanisms for activation of gCl are unknown.
Received 24 January 1995; accepted in final form 8 May 1995.
APS Manuscript Number G29-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.