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  • Several reports have shown that

    2022-08-05

    Several reports have shown that the ICD of CLRs is involved in the desensitization process of this superfamily. The analysis of our chimeric constructs between GlyRα1 and GLIC revealed differences in desensitization properties. In contrast, other ion channel properties such as channel block and ion selectivity are designated by regions outside of the ICD, e.g., the TM2-3 loop with interactions to pre-M1 [19]. Besides the large ICD, amino Walrycin B substitutions in the other intracellular TM1-2 loop identified in human patients suffering from the neuromotor disorder hyperekplexia have also been shown to drastically change desensitization properties of GlyRα1 [20]. In the GlyRα3 subunit, desensitization is influenced by the presence of a 15 amino acid insert in the TM3-4 loop resulting form alternative splicing events [12]. The fraction of desensitizing currents obtained for GlyRα1wt was small compared to the variant that lacks the ICD except both basic stretches at both ends. If basic stretches were separated by the GLIC ICD heptapeptide, receptors change back from fast desensitizing into slow desensitizing comparable to α1wt. Mutation of an arginine in the subdomain 423REVAR close to TM4 in 5HT3A also slowed down desensitization [21]. A recent study by Papke et al. reported large changes of entry into desensitization but almost no effect on deactivation when the GlyRα1 ICD was replaced by GLIC sequences supporting more evidence that the TM3-4 linker acts as site of posttranslational modulation of desensitization kinetics [5], [10].
    Acknowledgements
    Introduction Taurine (2-aminoethane sulfonic acid) is one of the most abundant amino acids in mammals [12], second in abundance only to glutamate [11]. Taurine has been considered one of the most important amino acids and is required for normal development of the nervous system [16], [18]. Additionally, it accumulates in the synaptosomal population [33] and in synaptic vesicles [31]. Reportedly, depletion of taurine causes a wide range of pathological conditions such as cardiomyopathy [41], loss of retinal photoreceptors [32], renal dysfunction [40], and retarded cell differentiation and migration in the cerebellum, visual cortex, and pyramidal cells, as has been demonstrated in monkeys and cats [17], [21], [35]. In addition, taurine is an important factor for adult neurogenesis [7]. In the hypothalamus, taurine is present throughout various nuclei [6]. Specifically, taurine is released by astrocytes in hypothalamic nuclei such as the supraoptic nucleus (SON) and paraventricular nucleus (PVN) [6] to regulate osmoregulation, providing tonic regulation of neuronal excitability [10]. In addition, taurine reportedly helps in the increase of vasopressin and oxytocin from the neural lobe of the magnocellular hypothalamo-neurohypophysial system [34]. Although several studies have analyzed the influence of taurine on the hypothalamic area and hormone release from the anterior hypothalamus, the present study elucidated the influence of taurine on preoptic hypothalamic area (PHA) neurons by examining the role of taurine on various neurotransmitter receptors using whole cell patch clamp electrophysiology.
    Materials and Methods
    Results
    Discussion Data from the present study suggest that taurine activates both synaptic and extrasynaptic glycine receptors in PHA neurons. Taurine-induced inward currents in PHA neurons were action potential independent. At higher concentrations such as 3mM, taurine can activate not only glycine, but also GABAA receptors in PHA neurons. Taurine promptly responds to osmotic stimuli for the regulation of cell volume and cell osmolarity [24], [25] and is a modulator of synaptic transmission by activating glycine and/or GABAA receptors depending on Walrycin B brain region [1], [8], [28], [39] and concentration [19]. In the present study, non-desensitizing activation of PHA neurons by taurine 0.5mM and complete blockade by strychnine provide clear evidence that at concentrations of 0.5mM taurine affect strychnine-sensitive glycine receptors in PHA neurons. Earlier studies have also discussed the strychnine sensitivity of taurine-induced currents in other human brain areas [38] and in the preoptic-anterior hypothalamus of rats [15]. Furthermore, taurine’s insensitivity to TTX, a Na+ channel blocker, highlighted the action potential-independent action of taurine-activated glycine receptors in PHA neurons. In addition, distributions of glycine-immunoreactive cell bodies [37] and fibers were found in the hypothalamus of the rat brain [30].