title: Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus.
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.
authors.affiliation: C. V. Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medical College, New York, New York 10065-4897, USA. faj2002@med.cornell.edu
authors.forename: Fan
authors.initials: F
authors.lastname: Jia
authors.forename: Minerva
authors.initials: M
authors.lastname: Yue
authors.forename: Dev
authors.initials: D
authors.lastname: Chandra
authors.forename: Angelo
authors.initials: A
authors.lastname: Keramidas
authors.forename: Peter A
authors.initials: PA
authors.lastname: Goldstein
authors.forename: Gregg E
authors.initials: GE
authors.lastname: Homanics
authors.forename: Neil L
authors.initials: NL
authors.lastname: Harrison
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D006801:Humans; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011963:Receptors, GABA-A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013654:Taurine / Q000494:pharmacology*; D013788:Thalamus / Q000166:cytology / Q000187:drug effects*; D014162:Transfection
chemical_list: C546260:GABRA4 protein, human; C546261:Gabra4 protein, mouse; D011963:Receptors, GABA-A; D013654:Taurine