title: Developmental shift in bidirectional functions of taurine-sensitive chloride channels during cortical circuit formation in postnatal mouse brain.
abstract: Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in the developing mammalian cerebral cortex, however, few studies have reported its neurobiological functions during development. In this study, by means of whole-cell patch-clamp recordings, we examined the effects of taurine on chloride channel receptors in neocortical neurons from early to late postnatal stages, which cover a critical period in cortical circuit formation. We show here that taurine activates chloride channels in cortical neurons throughout the postnatal stages examined (from postnatal day 2 to day 36). The physiological effects of taurine changed from excitatory to inhibitory due to variations in the intracellular Cl- concentration during development. An antagonist blocking analysis also demonstrated a developmental shift in the receptor target of taurine, from glycine receptors to GABAA receptors. Taken together, these results may reflect genetically programmed, bidirectional functions of taurine. At the early developmental stage, taurine acting on glycine receptors would serve to promote cortical circuit formation. As cortical circuit has to be regulated in the later stages, taurine would serve as a safeguard against hyperexcitable circuit.
authors.affiliation: Department of Integrated Biosciences, University of Tokyo, Bioscience Bldg. 402, Kashiwa, Chiba 277-8562, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Yoshida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Yusei
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Hisatsune
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D003423:Critical Period, Psychological; D004305:Dose-Response Relationship, Drug; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011247:Pregnancy; D011963:Receptors, GABA-A / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D013331:Strychnine / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D018756:GABA Antagonists; D018684:Glycine Agents; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D013654:Taurine; C017069:bicuculline methiodide; D013331:Strychnine; D001640:Bicuculline