Amino acid residues involved in agonist binding and its linking to channel gating, proximal to transmembrane domain of 5-HT3A receptor for halothane modulation / 대한마취과학회지
Korean Journal of Anesthesiology
; : 66-73, 2009.
Article
em En
| WPRIM
| ID: wpr-22035
Biblioteca responsável:
WPRO
ABSTRACT
BACKGROUND: The 5-hydroxytryptamine type 3 (5-HT3) receptor is a member of the Cys-loop superfamily of ligand-gated ion channels (LGICs) and modulated by pharmacologic relevant concentrations of volatile anesthetics or n-alcohols like most receptors of LGICs. The goal of this study was to reveal whether the site-directed single mutations of E-106, F-107 and R-222 in 5-HT3 receptor may affect the anesthetic modulation of halothane known as positive modulator. METHODS: The wild-type and mutant receptors, E106D, F107Y, R222F, R222V, were expressed in Xenopus Laevis oocytes and receptor function was assessed using two electrode voltage clamp techniques. RESULTS: E106D, F107Y, R222F, R222V mutant 5-HT3A receptors were functionally expressed. F107Y mutant 5-HT3A receptors displayed decreased sensitivity to 5-HT compared to the wild type 5-HT3A receptor (P < 0.05). Halothane showed positive modulation in both wild and F107Y mutant 5-HT3A receptors but F107Y mutant 5-HT3 receptor showed greater enhancing modulation comparing to wild-type receptor. Meanwhile, R222F and R222V mutant 5-HT3 receptor lost positive modulation with 1 and 2 MAC of halothane. Most interestingly, positive modulation by halothane was converted into negative modulation in E106D mutant 5-HT3A receptor. CONCLUSIONS: The present study implicate the amino acid residues known for agonist binding and linking agonist binding to channel gating might also have important role for anesthetic modulation in 5-HT3A receptor.
Palavras-chave
Texto completo:
1
Índice:
WPRIM
Assunto principal:
Oócitos
/
Xenopus laevis
/
Serotonina
/
Técnicas de Patch-Clamp
/
Receptores 5-HT3 de Serotonina
/
Eletrodos
/
Eletrofisiologia
/
Canais Iônicos de Abertura Ativada por Ligante
/
Halotano
/
Anestésicos
Idioma:
En
Revista:
Korean Journal of Anesthesiology
Ano de publicação:
2009
Tipo de documento:
Article