Department of Anesthesiology

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Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus.

TitleTaurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus.
Publication TypeJournal Article
Year of Publication2008
AuthorsJia F, Yue M, Chandra D, Keramidas A, Goldstein PA, Homanics GE, Harrison NL
JournalJ Neurosci
Volume28
Issue1
Pagination106-15
Date Published2008 Jan 2
ISSN1529-2401
KeywordsAnimals, Animals, Newborn, Cell Line, Transformed, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Electric Stimulation, Humans, Inhibitory Postsynaptic Potentials, Membrane Potentials, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Patch-Clamp Techniques, Receptors, GABA-A, Taurine, Thalamus, Transfection
Abstract

Taurine is one of the most abundant free amino acids in the brain. In a number of studies, taurine has been reported to activate glycine receptors (Gly-Rs) at moderate concentrations (> or = 100 microM), and to be a weak agonist at GABA(A) receptors (GABA(A)-Rs), which are usually activated at high concentrations (> or = 1 mM). In this study, we show that taurine reduced the excitability of thalamocortical relay neurons and activated both extrasynaptic GABA(A)-Rs and Gly-Rs in neurons in the mouse ventrobasal (VB) thalamus. Low concentrations of taurine (10-100 microM) decreased neuronal input resistance and firing frequency, and elicited a steady outward current under voltage clamp, but had no effects on fast inhibitory synaptic currents. Currents elicited by 50 microM taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 microM Zn2+, consistent with the pharmacological properties of extrasynaptic GABA(A)-Rs (alpha4beta2delta subtype) involved in tonic inhibition in the thalamus. Tonic inhibition was enhanced by an inhibitor of taurine transport, suggesting that taurine can act as an endogenous activator of these receptors. Taurine-evoked currents were absent in relay neurons from GABA(A)-R alpha4 subunit knock-out mice. The amplitude of the taurine current was larger in neurons from adult mice than juvenile mice. Taurine was a more potent agonist at recombinant alpha4beta2delta GABA(A)-Rs than at alpha1beta2gamma2 GABA(A)-Rs. We conclude that physiological concentrations of taurine can inhibit VB neurons via activation of extrasynaptic GABA(A)-Rs and that taurine may function as an endogenous regulator of excitability and network activity in the thalamus.

DOI10.1523/JNEUROSCI.3996-07.2008
Alternate JournalJ. Neurosci.
PubMed ID18171928
Grant ListAA 13004 / AA / NIAAA NIH HHS / United States
AA 16393 / AA / NIAAA NIH HHS / United States
GM 066840 / GM / NIGMS NIH HHS / United States
GM 47818 / GM / NIGMS NIH HHS / United States