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Regulation of tonic GABA inhibitory function, presympathetic neuronal activity and sympathetic outflow from the paraventricular nucleus by astroglial GABA transporters
Author(s) -
Park Jin Bong,
Jo Ji Yoon,
Zheng Hong,
Patel Kaushik P.,
Stern Javier E.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.173435
Subject(s) - rostral ventrolateral medulla , inhibitory postsynaptic potential , chemistry , tonic (physiology) , medicine , premovement neuronal activity , gabaergic , endocrinology , nipecotic acid , hypothalamus , efferent , nucleus , brainstem , neuroscience , bicuculline , gabaa receptor , neurotransmitter , biology , central nervous system , receptor , medulla oblongata , afferent
Neuronal activity in the hypothalamic paraventricular nucleus (PVN), as well as sympathetic outflow from the PVN, is basally restrained by a GABAergic inhibitory tone. We recently showed that two complementary GABA A receptor‐mediated modalities underlie inhibition of PVN neuronal activity: a synaptic, quantal inhibitory modality (IPSCs, I phasic ) and a sustained, non‐inactivating modality ( I tonic ). Here, we investigated the role of neuronal and/or glial GABA transporters (GATs) in modulating these inhibitory modalities, and assessed their impact on the activity of RVLM‐projecting PVN neurons (PVN‐RVLM neurons), and on PVN influence of renal sympathetic nerve activity (RSNA). Patch‐clamp recordings were obtained from retrogradely labelled PVN‐RVLM neurons in a slice preparation. The non‐selective GAT blocker nipecotic acid (100–300 μ m ) caused a large increase in GABA A I tonic , and reduced IPSC frequency. These effects were replicated by β‐alanine (100 μ m ), but not by SKF 89976A (30 μ m ), relatively selective blockers of GAT3 and GAT1 isoforms, respectively. Similar effects were evoked by the gliotoxin l ‐α‐aminodipic acid (2 m m ). GAT blockade attenuated the firing activity of PVN‐RVLM neurons. Moreover, PVN microinjections of nipecotic acid in the whole animal diminished ongoing RSNA. A robust GAT3 immunoreactivity was observed in the PVN, which partially colocalized with the glial marker GFAP. Altogether, our results indicate that by modulating ambient GABA levels and the efficacy of GABA A I tonic , PVN GATs, of a likely glial location, contribute to setting a basal tone of PVN‐RVLM firing activity, and PVN‐driven RSNA.