Publication
Taurine Is a Potent Activator of Extrasynaptic GABAAReceptors in the Thalamus
Publisher:
Society for Neuroscience
Date:
02-01-2008
DOI:
10.1523/JNEUROSCI.3996-07.2008
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 (≥100 μ m ), and to be a weak agonist at GABA A receptors (GABA A -Rs), which are usually activated at high concentrations (≥1 m m ). 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 μ m ) decreased neuronal input resistance and firing frequency, and elicited a steady outward current under voltage cl , but had no effects on fast inhibitory synaptic currents. Currents elicited by 50 μ m taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 μ m Zn 2+ , consistent with the pharmacological properties of extrasynaptic GABA A -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 GABA A -R α4 subunit knock-out mice. The litude of the taurine current was larger in neurons from adult mice than juvenile mice. Taurine was a more potent agonist at recombinant α4β2δ GABA A -Rs than at α1β2γ2 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.