Regulatory effects of GABA-A receptor trafficking and/or receptor phosphorylation on anesthetics

• Project/Area Number: 25670663
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Hirosaki University
• Principal Investigator: UENO Shinya 弘前大学, 医学(系)研究科(研究院), 教授 (00312158)
• Co-Investigator(Renkei-kenkyūsha): YAMADA Junko 弘前大学, 大学院医学研究科, 講師 (30334965) ; MIGITA Keisuke 弘前大学, 大学院医学研究科, 助教 (10352262) ; TOMIYAMA Masahiko 弘前大学, 大学院医学研究科, 客員研究員 (40311542)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: extrasynaptic GABA-A 受容体 / 受容体トラフィッキング / 脱リン酸化調節 / 受容体可視化 / extrasynaptic / GABA-A受容体 / 麻酔薬 / トラフィッキング

Outline of Final Research Achievements

The sensitivity to anesthetics was examined using transgenic mice with abnormal distribution of GABA-A receptors. Electrophysiological approach using slice patch clamp preparation demonstrated that anesthetics failed to enhance GABAergic response through extrasynaptic GABA-A receptors. Based on the evaluation of righting reflex, mice showed tolerance of anesthetics. Administration of dephosphorylation inhibitor cause these mice to recover the sensitivity to anesthetics. These result suggest that anesthetic effect could be regulated via trafficking and/or phosphorylation of GABA-A receptors.

Research Products

• [Journal Article] The kick-in system: a novel rapid knock-in strategy. (2014)
  • Author(s): Tomonoh, Y., Deshimaru, M., Araki, K., Miyazaki, Y., Arasaki, T., Tanaka, Y., Kitamura, H., Mori, F., Wakabayashi, K., Yamashita, S., Saito, R., Itoh, M., Uchida, T., Yamada, J., Migita, K., Ueno, S., Kitaura, H., Kakita, A., Lossin, C., Takano, Y., Hirose, S.
  • Journal Title: PLoS One. Volume: 9 Issue: 2 Pages: 88549-88549
  • DOI: 10.1371/journal.pone.0088549
  • Peer Reviewed / Open Access
• [Journal Article] Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motorcortex of a rat model of levodopa-induced dyskinesia. (2014)
  • Author(s): Ueno T, Yamada J, Nishijima H, Arai A, Migita K, Baba M, Ueno s, Tomiyama M.
  • Journal Title: Neurobiology of Disease Volume: 64 Pages: 142-9
  • DOI: 10.1016/j.nbd.2013.12.014
  • Peer Reviewed / Open Access
• [Journal Article] Morphologic changes of dendritic spines of striatal neurons in the levodopa-induced dyskinesia model (2014)
  • Author(s): Nishijima H, Suzuki S, Kon T, Funamizu Y, Ueno T, Haga R, Suzuki C, Arai A, Kimura T, Suzuki C, Meguro R, Miki Y, Yamada J, Migita K, Ichinohe N, Ueno S, Baba M, Tomiyama M
  • Journal Title: Mov Disord Volume: 29 Suppl 3 Issue: 3 Pages: 336-343
  • DOI: 10.1002/mds.25826
  • Peer Reviewed
• [Journal Article] Phospholipase C-related but catalytically inactive protein modulates pain behavior in a neuropathic pain model in mice (2013)
  • Author(s): Kitayama et al
  • Journal Title: Molecular Pain Volume: 9 Pages: 23-23
  • DOI: 10.1186/1744-8069-9-23
  • Peer Reviewed
• [Journal Article] Properties of a novel GABAA receptor gamma2 subunit mutation associated with seizures (2013)
  • Author(s): Migita, K. Yamada, J. Nikaido, Y. Shi, X. Kaneko, S. Hirose, S. Ueno, S.
  • Journal Title: J Pharmacol Sci Volume: 1 Pages: 84-87
  • Peer Reviewed
• [Journal Article] Drebrin immunoreactivity in the striatum of a rat model of levodopa-induced dyskinesia. (2013)
  • Author(s): Nishijima H, Arai A, Kimura T, Mori F, Yamada J, Migita K, Wakabayashi K, Baba M, Ueno S, Tomiyama M.
  • Journal Title: Neuropathology Volume: 33 Issue: 4 Pages: 391-6
  • DOI: 10.1111/neup.12009
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23241013
  • Peer Reviewed
• [Presentation] プロポフォールとエトミデートが麻酔脳波および睡眠・覚醒サイクルに与える影響 (2015)
  • Author(s): Yoshikazu, Nikaido, Sachie, Takada, Tomonori, Furukawa, Keisuke, Migita, Yuko, Shiba, Junko, Yamada, Tetsuya, Kushikata, Kazuyoshi, Hirota, Shuji, Shimoyama, Taku, Ozaki, Kazuhiko, Nakamura, Takashi, Kanematsu, Masato Hirata, Shinya, Ueno
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 前頭葉てんかんにおける新たな発症予防戦略 (2014)
  • Author(s): 上野伸哉
  • Organizer: 第48回 日本てんかん学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-02 – 2014-10-03
  • Invited
• [Presentation] 繰返し拘束ストレスに対するPRIP-1ノックアウトマウスの行動反応 (2014)
  • Author(s): Nikaido Y., Shimoyama S., Ozaki T., Migita K., Shiba Y., Furukawa T., Yamada J., Kanematsu T., Hirata M., Nakamura K. and Ueno S.
  • Organizer: 第37回日本神経科学会大会 Neuroscience 2014
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Repeated green odor exposure and chronic paroxetine treatment attenuate long-term behavioral alterations induced by delay fear conditioning in rats (2013)
  • Author(s): Nikaido Y., Yamada J., Migita K., Shiba Y., Nakashima T., Ueno S.
  • Organizer: 第54回日本神経学会
  • Place of Presentation: 京都
• [Presentation] The intracellular domain of the P2X7 receptor subunit participates in current facilitation and receptor kinetics (2013)
  • Author(s): Keisuke Migita, Junko Yamada, Yoshikazu Nikaido, Shinya Ueno
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego USA
• [Remarks] 弘前大学 大学院医学研究科 脳神経生理学講座
  • URL: http://www.med.hirosaki-u.ac.jp/~neurophysiol/