Receptor subtype specific effects of GABA agonists on neurons receiving aortic depressor nerve inputs within the nucleus of the solitary tract

Jing Zhang, Steven W. Mifflin

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42 Scopus citations

Abstract

The inhibitory amino acid gamma amino butyrate (GABA) has been shown to profoundly alter the integration of arterial baroreceptor inputs within the nucleus of the solitary tract (NTS). However, the relative roles of the major GABA receptor subtypes, the GABA(A) and the GABA(B) receptors, in the modulation of monosynaptic compared to polysynaptic afferent transmission within the NTS remain uncharacterized. In anesthetized rats, three types of NTS neuron were identified by their responses to aortic depressor nerve (ADN) stimulation; monosynaptic neurons (MSNs), polysynaptic neurons (PSNs) and ADN non-evoked neurons (NENs). Selective GABA(A) and GABA(B) agonists were applied to these neurons using iontophoretic techniques. The endogenous ligand GABA (2 mM), the selective GABA(A) agonist muscimol (0.04 and 0.02 mM) and the GABA(B) agonist baclofen (10 mM) all inhibited the spontaneous discharge of MSNs, PSNs and NENs (P<0.01 for each group). In addition, GABA, muscimol and baclofen also inhibited ADN evoked discharge in both MSNs and PSNs (P<0.05 for each group). Both GABA and baclofen significantly inhibited ADN evoked discharge in PSNs to a greater extent than in MSNs (P<0.05 for each comparison). Muscimol at both doses, however, similarly inhibited ADN evoked discharge in both MSNs and PSNs. Examination of action potential amplitude and co-iontophoretic application of glutamate and GABA agonists suggested that GABA and muscimol induced inhibition were likely to be post-synaptic in origin, while baclofen produced both pre-synaptic and post-synaptic inhibition, depending upon the cell. In conclusion, GABA can influence baroreceptor afferent integration through both pre-synaptic and post-synaptic mechanisms. Furthermore, the effects of GABA(B) agonists are variable depending upon the level of afferent integration, with MSNs being generally less sensitive than PSNs. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)170-181
Number of pages12
JournalJournal of the Autonomic Nervous System
Volume73
Issue number2-3
DOIs
StatePublished - 10 Nov 1998

Keywords

  • Baclofen
  • Baroreceptor
  • Central cardiovascular regulation
  • Iontophoresis
  • Muscimol

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