Elsevier

Brain Research

Volume 1021, Issue 2, 24 September 2004, Pages 232-240
Brain Research

Research report
Taurine activates strychnine-sensitive glycine receptors in neurons of the rat inferior colliculus

https://doi.org/10.1016/j.brainres.2004.07.001Get rights and content

Abstract

Taurine (Tau) is one of the most abundant free amino acids in the mammalian central nervous system. Whether the neurotransmission of the central auditory system is regulated or modulated by Tau is not clear. In the present study, we investigated the electrophysiological and pharmacological properties of Tau-activated currents in acutely dissociated neurons of the rat inferior colliculus (IC) using whole cell patch clamp recordings. At a holding potential of −60 mV and under a condition of chloride equilibrium potential near 0 mV, Tau activated an inward current and its half-maximal activation concentration was equal to 0.37 mM. The measured reversal potential of Tau-activated currents was close to theoretical chloride equilibrium potential. The currents evoked by Tau at both low (1 mM) and high (10 mM) concentrations were almost completely inhibited by strychnine, a glycine receptor antagonist. The Tau-activated current, however, was not affected by bicuculline, a GABAA receptor antagonist. Tau at increased concentrations progressively reduced the current response to subsequent glycine application. At saturated concentrations, Tau-activated current and glycine-activated current were mutually cross-desensitized by each other. These findings indicate that Tau activates glycine receptors in neurons of the rat IC and thus may have a functional role in regulating or modulating the neurotransmission of the central auditory system in mammals.

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).

References (60)

  • A.R. Kay et al.

    Isolation of neurons suitable for patch-clamping from adult mammalian central nervous systems

    J. Neurosci. Methods

    (1986)
  • O.A. Krishtal et al.

    Properties of glycine-activated conductances in rat brain neurones

    Neurosci. Lett.

    (1988)
  • S.M. Lasley

    Roles of neurotransmitter amino acids in seizure severity and experience in the genetically epilepsy-prone rat

    Brain Res.

    (1991)
  • D.A. Mathers et al.

    Membrane channels activated by taurine in cultured mouse spinal cord neurons

    Neurosci. Lett.

    (1989)
  • K. Murase et al.

    Serotonin suppresses N-methyl-d-aspartate responses in acutely isolated spinal dorsal horn neurons of the rat

    Brain Res.

    (1990)
  • K. Okamoto et al.

    Evidence for taurine as an inhibitory neurotransmitter in cerebellar stellate interneurons: selective antagonism by TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide)

    Brain Res.

    (1983)
  • M.H. Vallecalle-Sandoval et al.

    Comparison of the developmental changes of the brainstem auditory evoked response (BAER) in taurine-supplemented and taurine-deficient kittens

    Int. J. Dev. Neurosci.

    (1991)
  • D.S. Wang et al.

    Taurine-activated chloride currents in the rat sacral dorsal commissural neurons

    Brain Res.

    (1998)
  • J. Wang et al.

    Gamma-aminobutyric acid circuits shape response properties of auditory cortex neurons

    Brain Res.

    (2002)
  • L.J. Wu et al.

    A novel mechanical dissociation technique for studying acutely isolated maturing Drosophila central neurons

    J. Neurosci. Methods

    (2001)
  • G. Ye et al.

    Taurine inhibits rat substantia nigra pars reticulata neurons by activation of GABA- and glycine-linked chloride conductance

    Brain Res.

    (1997)
  • K.H. Backus et al.

    Glycine-activated currents are changed by coincident membrane depolarization in developing rat auditory brainstem neurones

    J. Physiol. (Lond.)

    (1998)
  • J. Broman

    Neurotransmitters in subcortical somatosensory pathways

    Anat. Embryol. (Berl.)

    (1994)
  • J.S. Buchwald et al.

    Far-field acoustic response: origins in the cat

    Science

    (1975)
  • J.H. Casseday et al.

    Neural tuning for sound duration: role of inhibitory mechanisms in the inferior colliculus

    Science

    (1994)
  • J.H. Casseday et al.

    Neural measurement of sound duration: control by excitatory–inhibitory interactions in the inferior colliculus

    J. Neurophysiol.

    (2000)
  • W.E. Davies et al.

    Taurine function in the auditory system

    Prog. Clin. Biol. Res.

    (1990)
  • W.E. Davies et al.

    The role of taurine in mammalian hearing

    Adv. Exp. Med. Biol.

    (1994)
  • W.E. Davies et al.

    The influence of different taurine diets on hearing development in normal babies. A preliminary report

    Adv. Exp. Med. Biol.

    (1996)
  • R.A. DeFazio et al.

    Potassium-coupled chloride cotransport controls intracellular chloride in rat neocortical pyramidal neurons

    J. Neurosci.

    (2000)
  • Cited by (18)

    • Inhibitory role of taurine in the caudal neurosecretory Dahlgren cells of the olive flounder, Paralichthys olivaceus

      2020, General and Comparative Endocrinology
      Citation Excerpt :

      Taurine regulates synaptic transmission, and activation of the GlyR or GABAAR varied from the brain region (Belluzzi et al., 2004; Puopolo et al., 1998) and taurine concentration (Hoang et al., 2013). It was believed that taurine activates GlyR rather than GABAAR in the mammalian CNS (Han et al., 2004). Furthermore, the interaction between taurine and glycine energy transmission system has also been confirmed.

    • Targeting inhibitory neurotransmission in tinnitus

      2012, Brain Research
      Citation Excerpt :

      Although CSF taurine increases are likely marginal, prolonged increases in taurine may achieve its physiological effect in the central nervous systems by mechanisms that fit this temporal profile. Synaptic GlyRs and GABAAR demonstrate faster desensitization rates and require higher concentrations of taurine for activation than thalamic extrasynaptic GABAARs agonists [and possibly uncharacterized tonically active extrasynaptic GlyRs (Wang et al., 2005; Xu et al., 2004, 2006)]. These extrasynaptic constructs would be sensitive to low level ambient increases in GABA [or glycine] and other selective agonists.

    • Interaction between taurine and GABA<inf>A</inf>/glycine receptors in neurons of the rat anteroventral cochlear nucleus

      2012, Brain Research
      Citation 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.

    • The effect of supplemental dietary Taurine on Tinnitus and auditory discrimination in an animal model

      2010, Hearing Research
      Citation Excerpt :

      Taurine has been shown to inhibit neural activity by acting at glycine (GlyR), GABAA (GABAAR), and GABAB (GABABR) receptors (Albrecht and Schousboe, 2005), and is distributed throughout the central and peripheral auditory system (Contreras and Bachelard, 1979; Harding and Davies, 1993). In the central auditory system it has been shown to activate GlyRs in rat inferior colliculus (IC) (Xu et al., 2004, 2006), and may act similarly in the auditory midbrain and brainstem, including the cochlear nucleus, superior olivary complex, and nuclei of the lateral lemniscus (Friauf et al., 1997). Although the inhibitory role of taurine is widespread in the CNS, it may have an excitatory role in the periphery.

    • Taurine in the anterior cingulate cortex diminishes neuropathic nociception: A possible interaction with the glycine<inf>A</inf> receptor

      2007, European Journal of Pain
      Citation 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.

    View all citing articles on Scopus
    View full text