Taurine Is a Potent Activator of Extrasynaptic GABA_AReceptors 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 (Ն100 M), and to be a weak agonist at GABA A receptors (GABA A -Rs), which are usually activated at high concentrations (Ն1 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 M) 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 M taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 M Zn 2ϩ , consistent with the pharmacological properties of extrasynaptic GABA A -Rs (␣4␤2␦ 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 ␣4␤2␦ GABA A -Rs than at ␣1␤2␥2 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.

Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of μ-opioid receptors

“…The results of these studies indicate that tonic conductance is a powerful regulator of individual excitability of mNTS neurons. These results are consistent with findings in the thalamus where taurine, an agonist of extrasynaptic GABA A receptors, has been shown to reduce the excitability of thalamocortical relay neurons (Jia et al 2008).…”

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…Recently, it has been demonstrated that GABA leading to tonic activation of GABA A receptors is released, at least in cerebellum, from glial cells by permeation through bestropin 1 anion channels (Lee et al, 2010). It has also been reported that taurine can activate extrasynaptic GABA A receptors in the mouse ventrobasal thalamus thus reducing the excitability of thalamocortical relay neurons (Jia et al, 2008).…”

Behavioral Changes and Survival in <i>Drosophila melanogaster</i>: Effects of Ascorbic Acid, Taurine, and Caffeine

“…19) Caffeine in energy drinks inhibits adenosine receptors and also increases levels of epinephrine, which can positively affect physical and mental performance. 20) We also demonstrated the dose-dependent effects of drink ingredients on locomotor activity in fruit flies, and showing that high levels of taurine and caffeine altered locomotor activity during both the subjective nighttime and daytime of the circadian rhythm (Fig.…”