title: Na(+) -Ca(2+) Exchanger, Leak K(+) Channel and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Comediate the Histamine-Induced Excitation on Rat Inferior Vestibular Nucleus Neurons.
abstract: OBJECTIVE
  Antihistaminergic drugs have traditionally been used to treat vestibular disorders in the clinic. As a potential central target for antihistaminergic drugs, the inferior vestibular nucleus (IVN) is the largest subnucleus of the central vestibular nuclear complex and is considered responsible for vestibular-autonomic responses and integration of vestibular, cerebellar, and multisensory signals. However, the role of histamine on the IVN, particularly the underlying mechanisms, is still not clear.
  
  
  METHODS
  Using whole-cell patch-clamp recordings on rat brain slices, histamine-induced effect on IVN neurons and the underlying receptor and ionic mechanisms were investigated.
  
  
  RESULTS
  We found that histamine remarkably depolarized both spontaneous firing neurons and silent neurons in IVN via both histamine H1 and histamine H2 receptors. Furthermore, Na(+) -Ca(2+) exchangers (NCXs) and background leak K(+) channels linked to H1 receptors and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to H2 receptors comediate the histamine-induced depolarization on IVN neurons.
  
  
  CONCLUSIONS
  These results demonstrate the multiple ionic mechanisms underlying the excitatory modulation of histamine/central histaminergic system on IVN neurons and the related vestibular reflexes and functions. The findings also suggest potential targets for the treatment of vestibular disorders in the clinic, at the level of ionic channels in central vestibular nuclei.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Shu-Liang
authors.initials: SL
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Shi-Yu
authors.initials: SY
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Deng-Yu
authors.initials: DY
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Jing-Ning
authors.initials: JN
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001593:Benzyl Compounds / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D018494:Histamine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology; D014726:Vestibular Nuclei / Q000166:cytology*
chemical_list: C487681:2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester; D001593:Benzyl Compounds; C568128:CNGA1 protein, rat; D002712:Chlorides; D054815:Cyclic Nucleotide-Gated Cation Channels; D018494:Histamine Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011743:Pyrimidines; D026941:Sodium Channel Blockers; D019831:Sodium-Calcium Exchanger; D053778:Thiazolidines; C082246:ICI D2788; D002586:Cesium; D013779:Tetrodotoxin; D006632:Histamine; C028019:cesium chloride
keywords: H1 receptors; H2 receptors; Histamine; Inferior vestibular nucleus; Ionic mechanisms