Lei Shen1, Wen-yu Cui2, Ru-zhu Chen1, Hai Wang2,3. 1. Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510085, China. 2. Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, China. 3. Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: 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. CONCLUSION: 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: Jared W Young; Nicola Crawford; John S Kelly; Lorraine E Kerr; Hugh M Marston; Christopher Spratt; Keith Finlayson; John Sharkey Journal: Eur Neuropsychopharmacol Date: 2006-05-02 Impact factor: 4.600
Authors: Fabiana Maria das Graças Corsi-Zuelli; Fernanda Brognara; Gustavo Fernando da Silva Quirino; Carlos Hiroji Hiroki; Rafael Sobrano Fais; Cristina Marta Del-Ben; Luis Ulloa; Helio Cesar Salgado; Alexandre Kanashiro; Camila Marcelino Loureiro Journal: Front Immunol Date: 2017-05-31 Impact factor: 7.561