PMID- 26806304
OWN - NLM
STAT- MEDLINE
DCOM- 20170110
LR  - 20181113
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 37
IP  - 3
DP  - 2016 Mar
TI  - Differential modulation of GABAA and NMDA receptors by alpha7-nicotinic receptor 
      desensitization in cultured rat hippocampal neurons.
PG  - 312-21
LID - 10.1038/aps.2015.106 [doi]
AB  - AIM: To explore the modulatory effect of desensitized alpha7-containing nicotinic 
      receptors (alpha7-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 alpha7-nAChR currents and to determine the role of 
      desensitized alpha7-nAChRs on brain amino acid receptor activity. RESULTS: Pulse and 
      perfusion applications of the alpha7-nAChR agonist choline were applied to induce 
      different types of alpha7-nAChR desensitization in cultured hippocampal neurons. 
      After a brief choline pulse, alpha7-nAChR was desensitized as a result of receptor 
      activation, which reduced the response of the A type gamma-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 alpha7-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 alpha7-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 alpha7-nAChR 
      as a result of choline pretreatment in cultured hippocampal neurons.
FAU - Shen, Lei
AU  - Shen L
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 
      Guangzhou 510085, China.
FAU - Cui, Wen-yu
AU  - Cui WY
AD  - Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 
      100039, China.
FAU - Chen, Ru-zhu
AU  - Chen RZ
AD  - Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 
      Guangzhou 510085, China.
FAU - Wang, Hai
AU  - Wang H
AD  - Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 
      100039, China.
AD  - Cardiovascular Drug Research Center, Institute of Health and Environmental 
      Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160125
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Choline/metabolism
MH  - Hippocampus/*cytology/metabolism
MH  - Neurons/cytology/*metabolism
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-A/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor/*metabolism
PMC - PMC4775840
EDAT- 2016/01/26 06:00
MHDA- 2017/01/11 06:00
PMCR- 2016/03/01
CRDT- 2016/01/26 06:00
PHST- 2015/07/30 00:00 [received]
PHST- 2015/10/26 00:00 [accepted]
PHST- 2016/01/26 06:00 [entrez]
PHST- 2016/01/26 06:00 [pubmed]
PHST- 2017/01/11 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - aps2015106 [pii]
AID - 10.1038/aps.2015.106 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2016 Mar;37(3):312-21. doi: 10.1038/aps.2015.106. Epub 2016 
      Jan 25.