RGD Reference Report - Modulation of neuronal nicotinic acetylcholine receptors by halothane in rat cortical neurons. - Rat Genome Database

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Modulation of neuronal nicotinic acetylcholine receptors by halothane in rat cortical neurons.

Authors: Mori, T  Zhao, X  Zuo, Y  Aistrup, GL  Nishikawa, K  Marszalec, W  Yeh, JZ  Narahashi, T 
Citation: Mori T, etal., Mol Pharmacol. 2001 Apr;59(4):732-43.
RGD ID: 8549520
Pubmed: PMID:11259617   (View Abstract at PubMed)

Inhalational general anesthetics have recently been shown to inhibit neuronal nicotinic acetylcholine (ACh) receptors (nnAChRs) expressed in Xenopus laevis oocytes and in molluscan neurons. However, drug actions on these systems are not necessarily the same as those seen on native mammalian neurons. Thus, we analyzed the detailed mechanisms of action of halothane on nnAChRs using rat cortical neurons in long-term primary culture. Currents induced by applications of ACh via a U-tube system were recorded by the whole-cell, patch-clamp technique. ACh evoked two types of currents, alpha-bungarotoxin-sensitive, fast desensitizing (alpha 7-type) currents and alpha-bungarotoxin-insensitive, slowly desensitizing (alpha 4 beta 2-type) currents. Halothane suppressed alpha 4 beta 2-type currents more than alpha 7-type currents with IC(50) values of 105 and 552 microM, respectively. Halothane shifted the ACh dose-response curve for the alpha 4 beta 2-type currents in the direction of lower ACh concentrations and slowed its apparent rate of desensitization. The rate of recovery after washout from halothane block was much faster than the rate of recovery from ACh desensitization. Thus, the halothane block was not caused by receptor desensitization. Chlorisondamine, an irreversible open channel blocker for nnAChRs, caused a time-dependent block that was attenuated by halothane. These results could be accounted for by kinetic simulation based on a model in which halothane causes flickering block of open channels, as seen in muscle nAChRs. Halothane block of nnAChRs is deemed to play an important role in anesthesia via a direct action on the receptor and an indirect action to suppress transmitter release.




Cellular Component

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Chrna4Ratacetylcholine-gated channel complex  IDA  RGD 
Chrna7Ratacetylcholine-gated channel complex  IDA  RGD 
Chrnb2Ratacetylcholine-gated channel complex  IDA  RGD 

Molecular Function

  


Genes (Rattus norvegicus)
Chrna4  (cholinergic receptor nicotinic alpha 4 subunit) Chrna7  (cholinergic receptor nicotinic alpha 7 subunit) Chrnb2  (cholinergic receptor nicotinic beta 2 subunit)