Journal of Neuroscience, Vol 15, 5025-5035, Copyright © 1995 by Society for Neuroscience
A presynaptic mechanism accounts for the differential block of nicotinic synapses on sympathetic B and C neurons by d-tubocurarine
WX Shen and JP Horn
Department of Neurobiology, University of Pittsburgh, School of Medicine, Pennsylvania 15261, USA.
The effects of d-tubocurarine (dTC) on nicotinic synapses on sympathetic B
and C neurons in the bullfrog were compared by recording trains of
postganglionic compound action potentials (CAPs) at 0.5-20 Hz. Block by dTC
was strongly use dependent in that the IC50 shifted almost 10-fold with
increasing stimulus frequency. Maximum sensitivity to dTC occurred at 5 Hz
in the B system and at 20 Hz in the C system. Recovery during posttrain
periods was characterized by transient reduction of CAP amplitude in the B
system and by transient enhancement of CAP amplitude in the C system. Thus,
dTC distinguished between nicotinic synapses on the two cell types. The
cell-specific effects of dTC could arise from differences in postsynaptic
or presynaptic nicotinic receptors, or from differences in acetylcholine
(ACh) release. We tested these possibilities using intracellular recording.
Based on comparison with iontophoretic responses to ACh, changes in EPSP
amplitude during repetitive stimulation in dTC could not be explained by
altered postsynaptic sensitivity. The block of nicotinic receptors was
further analyzed by recording synaptic currents. In B and C cells, 3 microM
dTC competitively antagonized EPSC amplitude by 54% without any sign of
open-channel block. In B cells, comparison of trains in normal Ringer and
dTC revealed a constant fractional reduction in EPSC amplitude, thereby
indicating that presynaptic nicotinic receptors do not influence release.
In the C system, dTC had no effect on peptidergic EPSPs, thereby suggesting
that presynaptic nicotinic receptors also do not influence peptide release.
We conclude that the differential effects of dTC on nicotinic transmission
are indirect consequences of differences in ACh release by preganglionic B
and C neurons.
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