title: Taurine protects against bilirubin-induced hyperexcitation in rat anteroventral cochlear nucleus neurons.
abstract: No effective medication for hyperbilirubinemia yet exists. Taurine is believed to exert a neuroprotective action. The aim of the present study was to determine whether taurine protected neurons of the rat anteroventral cochlear nucleus (AVCN) against bilirubin-induced neuronal hyperexcitation. AVCN neurons were isolated from 13 to 15-day-old Sprague-Dawley rats. The effects of bilirubin on the spontaneous excitatory postsynaptic currents (sEPSCs) and action potential currents were compared with those exerted by bilirubin and taurine together. Bilirubin dramatically increased the frequencies of sEPSCs and action potential currents, but not sEPSC amplitude. Taurine suppressed the enhanced frequency of action potentials induced by bilirubin, in a dose-dependent manner. In addition, taurine decreased the amplitude of voltage-dependent calcium channel currents that were enhanced upon addition of bilirubin. We explored the mechanism of the protective effects exerted by taurine using GABAA and glycine receptor antagonists, bicuculline and strychnine, respectively. Addition of bicuculline and strychnine eliminated the protective effects of taurine. Neither bilirubin nor taurine affected the sensitivity of the glutamate receptor. Our findings thus indicate that taurine protected AVCN neurons against bilirubin-induced neuronal hyperexcitation by activating the GABAA and glycine receptors and inhibiting calcium flow through voltage-gated channels. Thus, taurine may be effective in treatment of neonatal hyperbilirubinemia.
authors.affiliation: Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China; Department of Otorhinolaryngology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Ning-ying
authors.initials: NY
authors.lastname: Song
authors.affiliation: Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China. Electronic address: licycrystal@sina.com.
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Xin-lu
authors.initials: XL
authors.lastname: Yin
authors.affiliation: Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Hai-bo
authors.initials: HB
authors.lastname: Shi
authors.affiliation: Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Guo-ying
authors.initials: GY
authors.lastname: Han
authors.affiliation: Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China. Electronic address: yinshankai@china.com.
authors.forename: Shan-kai
authors.initials: SK
authors.lastname: Yin
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000633:toxicity; D001663:Bilirubin / Q000633:toxicity*; D015220:Calcium Channels / Q000502:physiology; D017626:Cochlear Nucleus / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006932:Hyperbilirubinemia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D018009:Receptors, Glycine / Q000502:physiology; D013654:Taurine / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D015220:Calcium Channels; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D013654:Taurine; D001663:Bilirubin
keywords: Bilirubin; GABA(A) receptor; Glycine receptor; Taurine; Voltage-dependent calcium channel currents