Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane

Kenji Seo, Hiroyuki Seino, Hiroyuki Yoshikawa, Andrey B. Petrenko, Hiroshi Baba, Naoshi Fujiwara, Genji Someya, Yoshiro Kawano, Takeyasu Maeda, Masato Matsuda, Takashi Kanematsu, Masato Hirata

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Potentiation of inhibitory γ-aminobutyric acid subtype A (GABAA) receptor function is involved in the mechanisms of anesthetic action. The present study examined the immobilizing action of the volatile anesthetic isoflurane in mice with double knockout (DKO) of phospholipase C-related inactive protein (PRIP)-1 and -2. Both of these proteins play important roles in the expression of GABAA receptors containing the γ2 subunit on the neuronal cell surface. Immunohistochemistry for GABAA receptor subunits demonstrated reduced expression of γ2 subunits in the spinal cord of the DKO mice. Immunohistochemistry also revealed up-regulation of the α1 and β3 subunits even though there were no apparent differences in the immunoreactivities for the β2 subunits between wild-type and DKO mice. The tail-clamp method was used to evaluate the anesthetic/immobilizing effect of isoflurane and the minimum alveolar concentration (MAC) was significantly lower in DKO mice compared with wild-type controls (1.07 ± 0.01% versus 1.36 ± 0.04% atm), indicating an increased sensitivity to isoflurane in DKO mice. These immunohistochemical and pharmacological findings suggest that reduced expression of the GABAA receptor γ2 subunit affects the composition and function of spinal GABAA receptors and potentiates the immobilizing action of isoflurane.

Original languageEnglish
Pages (from-to)1-4
Number of pages4
JournalNeuroscience Letters
Volume472
Issue number1
DOIs
Publication statusPublished - Mar 12 2010

Fingerprint

Isoflurane
GABA-A Receptors
Knockout Mice
Anesthetics
Immunohistochemistry
Aminobutyrates
Type C Phospholipases
Tail
Spinal Cord
Proteins
Up-Regulation
Pharmacology

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Seo, K., Seino, H., Yoshikawa, H., Petrenko, A. B., Baba, H., Fujiwara, N., ... Hirata, M. (2010). Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane. Neuroscience Letters, 472(1), 1-4. https://doi.org/10.1016/j.neulet.2010.01.031

Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane. / Seo, Kenji; Seino, Hiroyuki; Yoshikawa, Hiroyuki; Petrenko, Andrey B.; Baba, Hiroshi; Fujiwara, Naoshi; Someya, Genji; Kawano, Yoshiro; Maeda, Takeyasu; Matsuda, Masato; Kanematsu, Takashi; Hirata, Masato.

In: Neuroscience Letters, Vol. 472, No. 1, 12.03.2010, p. 1-4.

Research output: Contribution to journalArticle

Seo, K, Seino, H, Yoshikawa, H, Petrenko, AB, Baba, H, Fujiwara, N, Someya, G, Kawano, Y, Maeda, T, Matsuda, M, Kanematsu, T & Hirata, M 2010, 'Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane', Neuroscience Letters, vol. 472, no. 1, pp. 1-4. https://doi.org/10.1016/j.neulet.2010.01.031
Seo, Kenji ; Seino, Hiroyuki ; Yoshikawa, Hiroyuki ; Petrenko, Andrey B. ; Baba, Hiroshi ; Fujiwara, Naoshi ; Someya, Genji ; Kawano, Yoshiro ; Maeda, Takeyasu ; Matsuda, Masato ; Kanematsu, Takashi ; Hirata, Masato. / Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane. In: Neuroscience Letters. 2010 ; Vol. 472, No. 1. pp. 1-4.
@article{6a962fb4ff624b9e8db6062f74f74314,
title = "Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane",
abstract = "Potentiation of inhibitory γ-aminobutyric acid subtype A (GABAA) receptor function is involved in the mechanisms of anesthetic action. The present study examined the immobilizing action of the volatile anesthetic isoflurane in mice with double knockout (DKO) of phospholipase C-related inactive protein (PRIP)-1 and -2. Both of these proteins play important roles in the expression of GABAA receptors containing the γ2 subunit on the neuronal cell surface. Immunohistochemistry for GABAA receptor subunits demonstrated reduced expression of γ2 subunits in the spinal cord of the DKO mice. Immunohistochemistry also revealed up-regulation of the α1 and β3 subunits even though there were no apparent differences in the immunoreactivities for the β2 subunits between wild-type and DKO mice. The tail-clamp method was used to evaluate the anesthetic/immobilizing effect of isoflurane and the minimum alveolar concentration (MAC) was significantly lower in DKO mice compared with wild-type controls (1.07 ± 0.01{\%} versus 1.36 ± 0.04{\%} atm), indicating an increased sensitivity to isoflurane in DKO mice. These immunohistochemical and pharmacological findings suggest that reduced expression of the GABAA receptor γ2 subunit affects the composition and function of spinal GABAA receptors and potentiates the immobilizing action of isoflurane.",
author = "Kenji Seo and Hiroyuki Seino and Hiroyuki Yoshikawa and Petrenko, {Andrey B.} and Hiroshi Baba and Naoshi Fujiwara and Genji Someya and Yoshiro Kawano and Takeyasu Maeda and Masato Matsuda and Takashi Kanematsu and Masato Hirata",
year = "2010",
month = "3",
day = "12",
doi = "10.1016/j.neulet.2010.01.031",
language = "English",
volume = "472",
pages = "1--4",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane

AU - Seo, Kenji

AU - Seino, Hiroyuki

AU - Yoshikawa, Hiroyuki

AU - Petrenko, Andrey B.

AU - Baba, Hiroshi

AU - Fujiwara, Naoshi

AU - Someya, Genji

AU - Kawano, Yoshiro

AU - Maeda, Takeyasu

AU - Matsuda, Masato

AU - Kanematsu, Takashi

AU - Hirata, Masato

PY - 2010/3/12

Y1 - 2010/3/12

N2 - Potentiation of inhibitory γ-aminobutyric acid subtype A (GABAA) receptor function is involved in the mechanisms of anesthetic action. The present study examined the immobilizing action of the volatile anesthetic isoflurane in mice with double knockout (DKO) of phospholipase C-related inactive protein (PRIP)-1 and -2. Both of these proteins play important roles in the expression of GABAA receptors containing the γ2 subunit on the neuronal cell surface. Immunohistochemistry for GABAA receptor subunits demonstrated reduced expression of γ2 subunits in the spinal cord of the DKO mice. Immunohistochemistry also revealed up-regulation of the α1 and β3 subunits even though there were no apparent differences in the immunoreactivities for the β2 subunits between wild-type and DKO mice. The tail-clamp method was used to evaluate the anesthetic/immobilizing effect of isoflurane and the minimum alveolar concentration (MAC) was significantly lower in DKO mice compared with wild-type controls (1.07 ± 0.01% versus 1.36 ± 0.04% atm), indicating an increased sensitivity to isoflurane in DKO mice. These immunohistochemical and pharmacological findings suggest that reduced expression of the GABAA receptor γ2 subunit affects the composition and function of spinal GABAA receptors and potentiates the immobilizing action of isoflurane.

AB - Potentiation of inhibitory γ-aminobutyric acid subtype A (GABAA) receptor function is involved in the mechanisms of anesthetic action. The present study examined the immobilizing action of the volatile anesthetic isoflurane in mice with double knockout (DKO) of phospholipase C-related inactive protein (PRIP)-1 and -2. Both of these proteins play important roles in the expression of GABAA receptors containing the γ2 subunit on the neuronal cell surface. Immunohistochemistry for GABAA receptor subunits demonstrated reduced expression of γ2 subunits in the spinal cord of the DKO mice. Immunohistochemistry also revealed up-regulation of the α1 and β3 subunits even though there were no apparent differences in the immunoreactivities for the β2 subunits between wild-type and DKO mice. The tail-clamp method was used to evaluate the anesthetic/immobilizing effect of isoflurane and the minimum alveolar concentration (MAC) was significantly lower in DKO mice compared with wild-type controls (1.07 ± 0.01% versus 1.36 ± 0.04% atm), indicating an increased sensitivity to isoflurane in DKO mice. These immunohistochemical and pharmacological findings suggest that reduced expression of the GABAA receptor γ2 subunit affects the composition and function of spinal GABAA receptors and potentiates the immobilizing action of isoflurane.

UR - http://www.scopus.com/inward/record.url?scp=76949085944&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76949085944&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2010.01.031

DO - 10.1016/j.neulet.2010.01.031

M3 - Article

C2 - 20097266

AN - SCOPUS:76949085944

VL - 472

SP - 1

EP - 4

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 1

ER -