Research reportTaurine activates strychnine-sensitive glycine receptors in neurons of the rat inferior colliculus
Introduction
Taurine (Tau) is one of the most abundant free amino acids in the mammalian central nervous system and it has many putative cerebral functions [21]. Tau has been proposed as a possible inhibitory neurotransmitter in the substantia nigra [17], [22], [38], [39], [60], spinal cord [4], [35], [55], hippocampal CA1 area [59], and cerebellum [41]. In the auditory system, Tau is reported to be abundant in the inner ear [16], [18] and inferior colliculus (IC) of the auditory brainstem [15], [42]. Although under pathological conditions, such as seizures, there is a significant increase in the concentration of Tau in the IC [31], [45], [47], which signals a protective role of Tau. Several lines of evidence show that Tau is also an important substance for auditory functions and development [9], [10], [11], [43]. Tau supplement in diet has been reported to improve the maturation of the auditory brainstem response (ABR) in preterm infants and newborn kittens, as indicated by shorter latencies in the ABR and faster central conduction time [50], [53]. Because the major ABR waves originate from the auditory brainstem [5], [23], [34], those studies suggest a possibility that Tau may be involved in neural transmission and information processing of the central auditory pathways.
The functional role of Tau as a potential neuronal transmitter has been studied in a number of nervous systems other than the auditory system. Some studies indicate that the physiological actions of Tau upon neuronal receptors depend on the regions of the nervous system [6], [17], [55], [60]. In the young rat hippocampus [59], nucleus accumbens [24], and adult rat supraopic nucleus [20], Tau has been shown to activate only GlyRs at a low concentration but activate GABAARs as well at a high concentration. In the rat main olfactory bulb, Belluzzi et al. [3] demonstrate that Tau fails to activate GlyRs but activates GABAARs in mitral and tufted cells. In the mammalian dorsal root ganglion, Tau cannot activate GABAARs [46], [51], [52]. Electrophysiological experiments show that glycinergic inhibition and GABAergic inhibition converge in the same cells in the IC [7], [54] and that at least a subpopulation of IC neurons expresses both GlyRs and GABAARs [29]. However, it remains unclear whether or not the two types of receptors can be activated by Tau and what the electrophysiological role of Tau is, if any, in IC neurons.
In the present study, we studied the electrophysiological and pharmacological properties of Tau in acutely dissociated rat IC neurons using whole cell patch clamp recordings. Our results have shown that Tau can evoke currents (ITau) across the neuronal membrane in the IC neurons. We have further demonstrated that Tau activates strychnine (Str)-sensitive GlyRs in neurons of the rat IC.
Section snippets
Materials and methods
The use and care of animals in this study followed the guidelines and protocols approved by the Institutional Animal Care and Use Committee of the University of Science and Technology of China.
Cell identification
Among mechanically isolated cells from the ICC (Fig. 1B) of rats aged P10–P14, the medium-sized (10–20 μm in diameter) fusiform cells with oval or triangular soma were the most common. Those with one to three fine processes were identified as neurons (Fig. 2A). Under voltage clamp mode, the identified neurons often showed spontaneous postsynaptic currents (sPSCs) contributed by the adherent functional synaptic boutons (Fig. 2B) [1], [13] as evidence that the cells recorded were not likely glial
Discussion
The present study demonstrates that Tau, an abundant free amino acid present in the mammalian central nervous system, activates GlyRs rather than GABAARs (Fig. 6) under our experimental conditions and is a full agonist on GlyRs in this central auditory region (Fig. 3C). Our data show that GlyRs expressed in the IC neurons of young rats are less sensitive to Tau than to Gly, and the concentration range for ITau is broader than that of Gly (Fig. 3). The measured reversal potential of ITau in the
Acknowledgements
We thank Ms. You-Fei Ma and Dr. Long-Jun Wu for their critical reading of the manuscript. This study was supported by the National Natural Science Foundation of China (30270380) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2-SW-217).
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2012, Brain ResearchCitation Excerpt :There are a few studies that have examined the pharmacological specificity of taurine to GABAARs and GlyRs in central auditory nuclei. Taurine activates GlyRs in neurons of the auditory midbrain, inferior colliculus, and the auditory cortex (Tang et al., 2008; Xu et al., 2004). The taurine-activated currents in these neurons were almost entirely blocked by strychnine but not affected by bicuculline.
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2007, European Journal of PainCitation Excerpt :A possible explanation for the results of the experiments in which strychnine was administered prior to taurine or alone is that strychnine inhibits Cl− conductance in a channel associated with glyRA; this fact has been documented in an experiment carried out in hippocampal neurons (Mori et al., 2002). In a more recent communication by Xu et al. (2004), using a physiological and pharmacological approach, they demonstrate that a taurine activated current in inferior colliculus neurons is not affected by bicuculline (a GABAA receptor antagonist). This suggests that the action of taurine is exclusive of the glyRA, notwithstanding that both receptors have the same mechanism of action.