RT Journal Article
SR Electronic
T1 Taurine Is a Potent Activator of Extrasynaptic GABA<sub>A</sub> Receptors in the Thalamus
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 106
OP 115
DO 10.1523/JNEUROSCI.3996-07.2008
VO 28
IS 1
A1 Jia, Fan
A1 Yue, Minerva
A1 Chandra, Dev
A1 Keramidas, Angelo
A1 Goldstein, Peter A.
A1 Homanics, Gregg E.
A1 Harrison, Neil L.
YR 2008
UL http://www.jneurosci.org/content/28/1/106.abstract
AB 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 GABAA receptors (GABAA-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 GABAA-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 GABAA-Rs (α4β2δ 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 GABAA-R α4 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 α4β2δ GABAA-Rs than at α1β2γ2 GABAA-Rs. We conclude that physiological concentrations of taurine can inhibit VB neurons via activation of extrasynaptic GABAA-Rs and that taurine may function as an endogenous regulator of excitability and network activity in the thalamus.