Effect of cholinergic agonists on bulbospinal c1 neurons in the
rat.
Huangfu, Donghai, Ann M. Schreihofer, and Patrice G. Guyenet.
University of Virginia, Department of Pharmacology, Box 448 Health
Sciences Center, Charlottesville, VA 22908
APStracts 3:0281R, 1996.
Cholinergic inputs to the rostral ventrolateral medulla (RVLM) may
contribute to sympathetic tone generation. The present study analyzes
the response of RVLM neurons to cholinergic agonists. In chloralose
-anesthetized rats iontophoresis of carbachol excited RVLM
sympathoexcitatory neurons (+69% from resting level of 11.9+/-2
spikes/s; n=28). This effect was reduced 85% by iontophoresis of
methylatropine and abolished by i.v. scopolamine. Iontophoresis of
nicotine or hexamethonium was ineffective. In contrast, most RVLM
respiratory units were inhibited by carbachol. Whole-cell recordings
of bulbospinal RVLM neurons were made in neonatal rat brain slices
(54 cells, 24 C1 adrenergic neurons). In current clamp (without
tetrodotoxin) carbachol produced depolarization, increased PSP
frequency and decreased input resistance. In voltage clamp (-50 to
-60 mV;1 [mu]M tetrodotoxin) carbachol produced inward current (EC50:
10+/-1[mu]M; 12.6+/-2pA at 30[mu]M; n=16) that persisted in low
Ca++/high Mg++ (n=6). Muscarine (30[mu]M) caused smaller inward
currents (2.6+/-0.6pA; n=16). The carbachol-induced current was
reduced 46% by 5[mu]M methylatropine (n=15) and 84% by 200[mu]M
hexamethonium (n=9). The current was linear as a function of the
holding potential (extrapolated reversal potential: -22+/-2 mV). In
conclusion carbachol exerts both pre- and postsynaptic effects on C1
and other putative sympathoexcitatory RVLM neurons. In vitro, the
postsynaptic effect of carbachol has a mixed nicotinic and muscarinic
pharmacology. In vivo, iontophoretically applied carbachol produces
muscarinic excitation of barosensitive RVLM neurons.
Received 13 May 1996; accepted in final form 27 June 1996.
APS Manuscript Number R263-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996