title: Differential modulation of GABAA and NMDA receptors by α7-nicotinic receptor desensitization in cultured rat hippocampal neurons.
abstract: OBJECTIVE
  To explore the modulatory effect of desensitized α7-containing nicotinic receptors (α7-nAChRs) on excitatory and inhibitory amino acid receptors in cultured hippocampal neurons and to identify the mechanism underlying this effect.
  
  
  METHODS
  Whole-cell patch-clamp recordings were performed on cultured rat hippocampal neurons to measure α7-nAChR currents and to determine the role of desensitized α7-nAChRs on brain amino acid receptor activity.
  
  
  RESULTS
  Pulse and perfusion applications of the α7-nAChR agonist choline were applied to induce different types of α7-nAChR desensitization in cultured hippocampal neurons. After a brief choline pulse, α7-nAChR was desensitized as a result of receptor activation, which reduced the response of the A type γ-aminobutyric acid (GABAA) receptor to its agonist, muscimol, and enhanced the response of the NMDA receptor to its agonist NMDA. By contrast, the responses of glycine or AMPA receptors to their agonists, glycine or AMPA, respectively, were not affected. Pretreatment with the α7-nAChR antagonist methyllycaconitine (MLA, 10 nmol/L) blocked the choline-induced negative modulation of the GABAA receptor and the positive modulation of the NMDA receptor. The regulation of the GABAA and NMDA receptors was confirmed using another type of α7-nAChR desensitization, which was produced by a low concentration of choline perfusion. The negative modulation of the GABAA receptor was characterized by choline-duration dependency and intracellular calcium dependency, but the positive modulation of the NMDA receptor was not associated with cytoplasmic calcium.
  
  
  CONCLUSIONS
  Brain GABAA and NMDA receptors are modulated negatively and positively, respectively, by desensitized α7-nAChR as a result of choline pretreatment in cultured hippocampal neurons.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510085, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, China.
authors.forename: Wen-yu
authors.initials: WY
authors.lastname: Cui
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510085, China.
authors.forename: Ru-zhu
authors.initials: RZ
authors.lastname: Chen
authors.affiliation: Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, China.|Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002794:Choline