In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 295, No. 2 ( 2008-08), p. H807-H815
Abstract:
GABA B 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 GABA B 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 GABA B 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 GABA B 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 GABA B antagonist into the PVN increases sympathetic vasomotor tone in SHR, the GABA B antagonist did not affect EPSCs and IPSCs of the PVN neurons in vitro. These findings suggest that postsynaptic GABA B receptor function is upregulated in PVN presympathetic neurons in SHR. Whereas presynaptic GABA B receptor control of glutamatergic synaptic inputs is enhanced, presynaptic GABA B receptor control of GABAergic inputs in the PVN is attenuated in SHR. Changes in both pre- and postsynaptic GABA B receptors in the PVN may contribute to the control of sympathetic outflow in hypertension.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00259.2008
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
1477308-9
SSG:
12
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