Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane
| Autor: | Kenji Seo, Takeyasu Maeda, Masato Matsuda, Hiroyuki Yoshikawa, Naoshi Fujiwara, Hiroyuki Seino, Andrey B. Petrenko, Takashi Kanematsu, Masato Hirata, Yoshiro Kawano, Genji Someya, Hiroshi Baba |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Mice Knockout Minimum alveolar concentration Isoflurane GABAA receptor Chemistry General Neuroscience Protein subunit Intracellular Signaling Peptides and Proteins Long-term potentiation Pharmacology Receptors GABA-A Inhibitory postsynaptic potential Mice Inbred C57BL Immobilization Mice Spinal Cord Anesthetics Inhalation Anesthetic medicine Animals Receptor Adaptor Proteins Signal Transducing medicine.drug |
| Zdroj: | Neuroscience Letters. 472:1-4 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2010.01.031 |
| Popis: | Potentiation of inhibitory gamma-aminobutyric acid subtype A (GABA(A)) 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 GABA(A) receptors containing the gamma2 subunit on the neuronal cell surface. Immunohistochemistry for GABA(A) receptor subunits demonstrated reduced expression of gamma2 subunits in the spinal cord of the DKO mice. Immunohistochemistry also revealed up-regulation of the alpha1 and beta3 subunits even though there were no apparent differences in the immunoreactivities for the beta2 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 GABA(A) receptor gamma2 subunit affects the composition and function of spinal GABA(A) receptors and potentiates the immobilizing action of isoflurane. |
| Databáze: | OpenAIRE |
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