Plasticity of pre- and postsynaptic GABAB receptor function in the paraventricular nucleus in spontaneously hypertensive rats

De Pei Li, Qing Yang, Hao Min Pan, Hui Lin Pan

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

GABAB receptor function is upregulated in the paraventricular nucleus (PVN) of the hypothalamus in spontaneously hypertensive rats (SHR), but it is unclear whether this upregulation occurs pre- or postsynaptically. We therefore determined pre- and postsynaptic GABAB receptor function in retrogradely labeled spinally projecting PVN neurons using whole cell patch-clamp recording in brain slices in SHR and Wistar-Kyoto (WKY) rats. Bath application of the GABAB receptor agonist baclofen significantly decreased the spontaneous firing activity of labeled PVN neurons in both SHR and WKY rats. However, the magnitude of reduction in the firing rate was significantly greater in SHR than in WKY rats. Furthermore, baclofen produced larger membrane hyperpolarization and outward currents in labeled PVN neurons in SHR than in WKY rats. The baclofen-induced current was abolished by either including G protein inhibitor GDPβS in the pipette solution or bath application of the GABAB receptor antagonist in both SHR and WKY rats. Blocking N-methyl-D-aspartic acid receptors had no significant effect on baclofen-elicited outward currents in SHR. In addition, baclofen caused significantly greater inhibition of glutamatergic excitatory postsynaptic currents (EPSCs) in labeled PVN neurons in brain slices from SHR than WKY rats. By contrast, baclofen produced significantly less inhibition of GABAergic inhibitory postsynaptic currents (IPSCs) in labeled PVN neurons in SHR than in WKY rats. Although microinjection of the GABAB antagonist into the PVN increases sympathetic vasomotor tone in SHR, the GABAB antagonist did not affect EPSCs and IPSCs of the PVN neurons in vitro. These findings suggest that postsynaptic GABAB receptor function is upregulated in PVN presympathetic neurons in SHR. Whereas presynaptic GABAB receptor control of glutamatergic synaptic inputs is enhanced, presynaptic GABAB receptor control of GABAergic inputs in the PVN is attenuated in SHR. Changes in both pre- and postsynaptic GABAB receptors in the PVN may contribute to the control of sympathetic outflow in hypertension.

Original languageEnglish (US)
Pages (from-to)H807-H815
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number2
DOIs
StatePublished - Aug 2008

Keywords

  • Autonomic nervous system
  • Baclofen
  • Hypertension
  • Synaptic transmission
  • γ-aminobutyric acid

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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