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The Journal of Neuroscience, January 2, 2008, 28(1):106-115; doi:10.1523/JNEUROSCI.3996-07.2008

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Cellular/Molecular
Taurine Is a Potent Activator of Extrasynaptic GABA_A Receptors in the Thalamus

Fan Jia,¹ Minerva Yue,¹ Dev Chandra,^2,3 Angelo Keramidas,¹ Peter A. Goldstein,¹ Gregg E. Homanics,^2,3 and Neil L. Harrison¹

¹C. V. Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, New York, New York 10065-4897, and Departments of ²Anesthesiology and ³Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Correspondence should be addressed to either Dr. Fan Jia or Dr. Neil L. Harrison, Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, Room A-1050, New York, NY 10065-4897. Email: faj2002{at}med.cornell.edu or Email: neh2001{at}med.cornell.edu

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 (100 µM), and to be a weak agonist at GABA_A receptors (GABA_A-Rs), which are usually activated at high concentrations (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 µM) 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 µM taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 µM Zn²⁺, consistent with the pharmacological properties of extrasynaptic GABA_A-Rs (4β2 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 4 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 4β2 GABA_A-Rs than at 1β22 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.

Key words: 4 subunit; tonic inhibition; synaptic transmission; VB; ion channel; glycine receptor

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Received July 12, 2007; revised Nov. 13, 2007; accepted Nov. 14, 2007.

Correspondence should be addressed to either Dr. Fan Jia or Dr. Neil L. Harrison, Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, Room A-1050, New York, NY 10065-4897. Email: faj2002{at}med.cornell.edu or Email: neh2001{at}med.cornell.edu

This article has been cited by other articles:

				F. Jia, D. Chandra, G. E. Homanics, and N. L. Harrison Ethanol Modulates Synaptic and Extrasynaptic GABAA Receptors in the Thalamus J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 475 - 482. [Abstract] [Full Text] [PDF]

				A. Keramidas and N. L. Harrison Agonist-dependent Single Channel Current and Gating in {alpha}4{beta}2{delta} and {alpha}1{beta}2{gamma}2S GABAA Receptors J. Gen. Physiol., January 28, 2008; 131(2): 163 - 181. [Abstract] [Full Text] [PDF]

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