Activation of gabab receptors increases a potassium conductance in
rat bulbospinal neurons of the c1 area.
Li, Yu-Wen, and Patrice G. Guyenet.
University of Virginia, Department of Pharmacology, Box 448 Health
Sciences Center, Charlottesville, VA 22908
APStracts 3:0163R, 1996.
In anesthetized rats iontophoresis of the GABAB receptor agonist and
antispastic drug baclofen inhibits the bulbospinal vasomotor neurons
of the rostral ventrolateral medulla (RVLM) (16). The present study
was carried out to determine if C1 adrenergic and other bulbospinal
neurons of the RVLM have postsynaptic GABAB receptors. Retrogradely
labeled RVLM bulbospinal neurons (n=52) were recorded in 120[mu]m
-thick slices from neonatal rat brain (3-10 day-old). Most neurons
(48/52) were tonically active (3+/-0.6 spikes/s). Twenty-six neurons
were recovered histologically and 18 of them were immunoreactive for
tyrosine hydroxylase (TH). In current-clamp, baclofen (0.3-10 [mu]M)
hyperpolarized RVLM bulbospinal cells in a dose-dependent manner
(16+/-0.5 mV hyperpolarization by 3 [mu]M baclofen; n=19) and
decreased input resistance by 40% (n=10). In voltage-clamp (1 [mu]M
TTX present; holding potential: -40 to -60 mV), 3 [mu]M baclofen
induced an outward current of 21+/-2 pA (n=29). This current
exhibited inward rectification and reversed polarity close to the
potassium equilibrium potential ([K+]o from 2.5 to 10mM). The current
induced by baclofen was reduced 90% by 0.1-0.2 mM BaCl2 (n=6) and was
blocked reversibly by the selective GABAB receptor antagonist CGP
-55845A (0.5-1 [mu]M; n=6). All histologically verified TH
-immunoreactive cells (n=18) were sensitive to baclofen. In summary,
RVLM bulbospinal neurons including C1 adrenergic cells possess GABAB
receptors. Activation of these receptors increases an inwardly
rectifying potassium conductance. This effect reduces the intrinsic
firing frequency of RVLM vasomotor neurons "in vitro" and may
contribute to the sympatholytic action of baclofen "in vivo".
Received 27 November 1995; accepted in final form 22 April 1996.
APS Manuscript Number R744-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96