From: John P. Horn (jph+@pitt.edu)
Date: Wed Apr 12 2000 - 06:58:51 MDT
Our new paper focuses on the interaction between metabotropic excitation and
fast epsps.
A Model for Pleiotropic Muscarinic Potentiation of Fast Synaptic
Transmission
J. Neurophysiol. 2000 83: 1912-1923.
Hermann Schobesberger, Diek W. Wheeler, and John P. Horn
http://jn.physiology.org/cgi/content/full/83/4/1912
Abstract
The predominant form of muscarinic excitation in the forebrain and in
sympathetic ganglia arises from m1 receptors coupled to the Gq/11 signal
transduction pathway. Functional components of this system have been most
completely mapped in frog sympathetic B neurons. Presynaptic stimulation of
the B neuron produces a dual-component muscarinic excitatory postsynaptic
potential (EPSP) mediated by suppression of voltage-dependent M-type K+
channels and activation of a voltage-insensitive cation current. Evidence
from mammalian systems suggests that the cation current is mediated by
cyclic GMP-gated channels. This paper describes the use of a computational
model to analyze the consequences of pleiotropic muscarinic signaling for
synaptic integration. The results show that the resting potential of B
neurons is a logarithmic function of the leak conductance over a broad range
of experimentally observable conditions. Small increases (<4 nS) in the
muscarinically regulated cation conductance produce potent excitatory
effects. Damage introduced by intracellular recording can mask the
excitatory effect of the muscarinic leak current. Synaptic activation of the
leak conductance combines synergistically with suppression of the
M-conductance (from 40 to 20 nS) to strengthen fast nicotinic transmission.
Overall, this effect can more than double synaptic strength, as measured by
the ability of a fast nicotinic EPSP to trigger an action potential.
Pleiotropic muscarinic excitation can also double the temporal window of
summation between subthreshold nicotinic EPSPs and thereby promote firing.
Activation of a chloride leak or suppression of a K+ leak can substitute for
the cation conductance in producing excitatory muscarinic actions. The
results are discussed in terms of their implications for synaptic
integration in sympathetic ganglia and other circuits.
John P. Horn, Ph.D.
Department of Neurobiology
University of Pittsburgh
School of Medicine
Pittsburgh, PA 15261
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