Functional roles of leak K+ channels in injured motoneurons

• Project/Area Number: 21700432
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurophysiology and muscle physiology
• Research Institution: Osaka University
• Principal Investigator: TOYODA Hiroki Osaka University, 大学院・歯学研究科, 講師 (00432451)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 漏洩K^+チャネル / ニューロン / 一酸化窒素 / 漏洩カリウムチャネル / 神経損傷 / 神経麻痺 / リークカリウムチャネル

Research Abstract

It is known that production of nitric oxide (NO) is enhanced in injured motoneurons after peripheral nerve injury, The enhanced NO production is thought to contribute to the occurrence of nerve paralysis, However, it remains unknown how the enhanced NO production induces nerve paralysis, In this study, I focused on the changes in the membrane excitability by NO as the mechanism of neural paralysis, In particular, I studied on the NO-mediated modulation of leak K^+ currents, which regulate the resting membrane potential and the input resistance, Following application of 8-Br-cGMP, leak K^+ currents were decreased in large-sized motoneurons, while those were increased in small-sized motoneurons, These results suggest that activation of NO-cGMP-PKG pathway alters the membrane excitability of motoneurons through modulating the leak K^+ currents, It is possible that such neural mechanisms are involved in the occurrence of neural paralysis,

Research Products

• [Journal Article] PKG dynamically modulates TASK1-mediated leak K+ currents in cholinergic neurons of the basal forebrain (2010)
  • Author(s): Toyoda H, Saito M, Okazawa M, Hirao K, Sato H, Abe H, Takada K, Funabiki K, Takada M, Kaneko T, Kang, Y
  • Journal Title: Journal of Neuroscience 30 Pages: 5677-5689
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-dependent kinase IV contributes to translation-dependent early synaptic potentiation in the anterior cingulate cortex of adult mice (2010)
  • Author(s): Toyoda H, Zhao MG, Mercaldo V, Chen T, Descalzi G, Kida S, Zhuo M
  • Journal Title: Molecular Brain 3 Pages: 27-27
  • Peer Reviewed
• [Journal Article] Rank-ordered recruitment of masseter motoneurons by the activity of mesencephalic trigeminal neurons during slow closing phase of mastication cycle (2010)
  • Author(s): Kang Y, Saito M, Toyoda H, Sato H
  • Journal Title: Journal of Oral Bioscience 52(4) Pages: 330-335
  • Peer Reviewed
• [Journal Article] Protein kinase G dynamically modulates TASK1-mediated leak K^+ currents in cholinergic neurons of the basal forebrain. (2010)
  • Author(s): Toyoda, H., et al.
  • Journal Title: Journal of Neuroscience Volume: 30(16) Pages: 5677-5689
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-dependent kinase IV contributes to translation-dependent early synaptic potentiation in the anterior cingulate cortex of adult mice. (2010)
  • Author(s): Toyoda, H., et al.
  • Journal Title: Molecular Brain Volume: 27
  • Peer Reviewed
• [Journal Article] Rank-ordered recruitment of masseter motoneurons by the activity of mesencephalic trigeminal neurons during slow closing phase of mastication cycle. (2010)
  • Author(s): Kang, Y., et al.
  • Journal Title: Journal of Oral Bioscience Volume: 52 Pages: 330-335
  • Peer Reviewed
• [Journal Article] Roles of the AMPA receptor subunit GluA1 but not GluA2 in synaptic potentiation and activation of ERK in the anterior cingulate cortex (2009)
  • Author(s): Toyoda H, Zhao MG, Ulzhofer B, Wu LJ, Xu H, Seeburg PH, Sprengel R, Kuner R, Zhuo M
  • Journal Title: Molecula, Pain 5 Pages: 46-46
  • Peer Reviewed
• [Journal Article] Rapid use-dependent down-regulation of γ-aminobutyric acid type A receptors in rat mesencephalic trigeminal neurons (2009)
  • Author(s): Saito M, Toyoda H, Sato H, Ishii Y, Kang Y
  • Journal Title: Journal of Neuroscience Research 87 Pages: 3120-3133
  • Peer Reviewed
• [Journal Article] Enhanced synaptic long-term potentiation in the anterior cingulate cortex of adult wild mice as compared with that in laboratory mice (2009)
  • Author(s): Zhao MG, Toyoda H, Wang YK, Zhuo M
  • Journal Title: Molecular Brain 2 Pages: 11-11
  • Peer Reviewed
• [Journal Article] Enhanced quantal release of excitatory transmitter in anterior cingulate cortex of adult mice with chronic pain (2009)
  • Author(s): Toyoda H, Zhao MG, Zhuo M
  • Journal Title: Molecular Pain 5 Pages: 4-4
  • Peer Reviewed
• [Journal Article] Enhanced synaptic long-term potentiation in the interior cingulate cortex of adult wild mice as compared with that in laboratory mice. (2009)
  • Author(s): Zhao, M.G., et al.
  • Journal Title: Molecular Brain 11
  • Peer Reviewed
• [Journal Article] Rapid Use-Dependent Down-Regulation of γ-Aminobutyric Acid Type A Receptors in Rat Mesencephalic Trigeminal Neurons (2009)
  • Author(s): Saito, M., et al.
  • Journal Title: Journal of Neuroscience ReSCarch 87 Pages: 3120-3133
  • Peer Reviewed
• [Journal Article] Roles of the AMPA receptor subunit GluA1 but not GluA2 in synaptic potentiation and activation of ERK in the anterior cingulate cortex (2009)
  • Author(s): Toyoda, H., et al.
  • Journal Title: Molecular Pain 46
  • Peer Reviewed
• [Presentation] Bidirectional regulation of TASK1 channels expressed in HEK cells by modulation of PKG (2011)
  • Author(s): 豊田博紀, 齋藤充, 岡澤慎, 平尾圭子, 佐藤元, 阿部遙, 高田健治, 船曳和雄, 高田昌彦, 金子武嗣, 姜英男
  • Organizer: 第88回日本生理学会大会・第116回日本解剖学会総会全国学術集会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-28
• [Presentation] Intercolumnar and intracolumnar desynchronization by GABAB receptor-mediated presynaptic inhibition in the rat barrel cortex. (2011)
  • Author(s): 齋藤充, 佐藤元, 豊田博紀, 田中琢真, 小林真之, Daniel Althof, Akos Kulik, 青柳富誌生, 重本隆一, 姜英男
  • Organizer: 第88回日本生理学会大会・第116回日本解剖学会総会全国学術集会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-28
• [Presentation] Differential electrophysiological properties of capsaicin-induced currents between layer II/III and layer V pyramidal cells of the insular cortex. (2011)
  • Author(s): 佐藤元, 川上晋平, 豊田博紀, 齋藤充, Yong-Chul Bae, 姜英男
  • Organizer: 第88回日本生理学会大会・第116回日本解剖学会総会全国学術集会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-28
• [Presentation] Bidirectional regulation of TASK1 channels expressed in HEK cells by modulation of PKG (2011)
  • Author(s): 豊田博紀, 他
  • Organizer: 第88回日本生理学会大会・第116回日本解剖学会総会全国学術集会 合同大会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-03-28
• [Presentation] Membrane hyperpolarization depresses AMPA currents in the primary sensory neuron of the rat mesencephalic trigeminal nucleus. (2010)
  • Author(s): Kawasaki Y, Saito M, Toyoda H, Sato H, Tanaka S, Kogo M, Kang Y.
  • Organizer: 40th Society for Neuroscience
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2010-11-17
• [Presentation] Protein kinase G (PKG) bidirectionally modulates TASK1 currents in PKG-loaded HEK 293 cells. (2010)
  • Author(s): Toyoda H, Saito M, Okazawa M, Hirao K, Sato H, Abe H, Takada K, Funabiki K, Takada M, Kaneko T, Kang Y.
  • Organizer: 40th Society for Neuroscience
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2010-11-15
• [Presentation] Inter-and intracolumnar desynchronization by presynaptic GABAB inhibition in the rat barrel cortex. (2010)
  • Author(s): Saito M, Sato H, Toyoda H, Kobayashi M, Althof D, Kulik A, Shigemoto R, Kang Y.
  • Organizer: 40th Society for Neuroscience
  • Place of Presentation: San Diego,USA.
  • Year and Date: 2010-11-15
• [Presentation] PKG bidirectionally modulates TASK1 currents in PKG-loaded HEK 293 cells. (2010)
  • Author(s): Toyoda, H., et al.
  • Organizer: 40th Society for Neuroscience
  • Place of Presentation: San Diego Convention Center (San Diego, USA)
  • Year and Date: 2010-11-15
• [Presentation] Electrophysiological properties of capsaicin-induced currents in layer II/III and layer V pyramidal cells of the insular cortex. (2010)
  • Author(s): Sato H, Kawakami S, Toyoda H, Saito M, Bae YC, Kang Y.
  • Organizer: 40th Society for Neuroscience
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2010-11-13
• [Presentation] カプサイシン投与により島皮質において誘発されるnetwork oscillation (2010)
  • Author(s): 佐藤元, 豊田博紀, 齋藤充, 姜英男
  • Organizer: 第103回近畿生理学談話会
  • Place of Presentation: 吹田
  • Year and Date: 2010-10-02
• [Presentation] 三叉神経中脳路核ニューロンにおいてグルタミン酸作動性入力を無効化するイオン機構 (2010)
  • Author(s): 川嵜康大, 齋藤充, 佐藤元, 豊田博紀, 姜英男
  • Organizer: 第103回近畿生理学談話会
  • Place of Presentation: 吹田
  • Year and Date: 2010-10-02
• [Presentation] Bidirectional modulation of leak K+ currents by PKG in cholinergic neurons of the basal forebrain. (2009)
  • Author(s): Toyoda H, Saito M, Hirao K, Sato H, Takada K, Kaneko T, Kang Y.
  • Organizer: 39th Society for Neuroscience
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2009-10-21
• [Presentation] PKG modulates the recruitment of masseter motoneurons caused by the presumed spindle Ia inputs. (2009)
  • Author(s): Sato M, Saito M, Toyoda H, Kang Y.
  • Organizer: 39th Society for Neuroscience
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2009-10-21
• [Presentation] Bidirectional modulation of leak K^+ currents by PKG in cholinergic neurons of the basal forebrain (2009)
  • Author(s): Toyoda, H., et al.
  • Organizer: 39th Society for Neuroscience
  • Place of Presentation: MeCormiek Place (Chicago, USA)
  • Year and Date: 2009-10-21
• [Presentation] Inter- and intra-columnar desynchronization of excitatory input by presynaptic GABAB inhibition in the rat barrel cortex. (2009)
  • Author(s): Saito M, Sato M, Toyoda H, Kang Y.
  • Organizer: 39th Society for Neuroscience
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2009-10-20
• [Presentation] 咬筋運動ニューロンにおける漏洩K+電流に対するPKGの調節作用 (2009)
  • Author(s): 豊田博紀, 平尾圭子, 齋藤充, 佐藤元, 姜英男
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-16
• [Presentation] 咬筋運動ニューロンにおけるTASKチャネルの発現様式 (2009)
  • Author(s): 平尾圭子, 豊田博紀, 齋藤充, 佐藤元, 姜英男
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-16
• [Presentation] 咬筋運動ニューロンにおける漏痩K(+)電流に対するPKGの調節作用 (2009)
  • Author(s): 豊田博紀, 他
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2009-09-16
• [Presentation] 咬筋運動ニューロンにおける漏洩K+電流のPKGによる動的調節 (2009)
  • Author(s): 豊田博紀, 平尾圭子, 齋藤充, 佐藤元, 姜英男
  • Organizer: 第51回歯科基礎医学会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-11
• [Presentation] 咬筋運動ニューロンにおける漏洩K(+)電流のPKGによる動的調節 (2009)
  • Author(s): 豊田博紀, 他
  • Organizer: 第51回歯科基礎医学会
  • Place of Presentation: 朱鷺メッセ:新潟コンベンションセンター(新潟)
  • Year and Date: 2009-09-11
• [Presentation] 閉口筋運動ニューロンの序列動員とPKGによるその修飾 (2009)
  • Author(s): 齋藤充, 佐藤元, 深津雄己, 豊田博紀, 姜英男
  • Organizer: 第51回歯科基礎医学会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-10
• [Presentation] 大脳皮質バレル野と味覚野におけるカラム情報処理機構の領野特異性 (2009)
  • Author(s): 佐藤元, 齋藤充, 豊田博紀, 姜英男
  • Organizer: 第51回歯科基礎医学会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-10
• [Presentation] Recruitment of masseter motoneurons by the presumed spindle Ia inputs. (2009)
  • Author(s): Sato H, Saito M, Toyoda H, Kang Y.
  • Organizer: XXXVI International Congress of Physiological Sciences
  • Place of Presentation: Kyoto.
  • Year and Date: 2009-07-30
• [Presentation] PKG modulates TASK1-like currents in cholinergic neurons of the basal forebrain. (2009)
  • Author(s): Toyoda H, Saito M, Hirao K, Sato H, Takada K, Kaneko T, Kang Y.
  • Organizer: XXXVI International Congress of Physiological Sciences
  • Place of Presentation: Kyoto.
  • Year and Date: 2009-07-29
• [Presentation] Presynaptic GABAB inhibition involved in the inter- and intra-columnar desynchronization of glutamatergic input in the rat barrel cortex. (2009)
  • Author(s): Saito M, Sato H, Toyoda H, Kang Y.
  • Organizer: XXXVI International Congress of Physiological Sciences
  • Place of Presentation: Kyoto.
  • Year and Date: 2009-07-29
• [Presentation] PKG modulates TASK1-like currents in cholinergic neurons of the basal forebrain (2009)
  • Author(s): Toyoda, H., et al.
  • Organizer: XXXVI International Congress of Physiological Sciences
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2009-07-29
• [Book] Recruitment of masseter motoneurons by the presumed spindle Ia inputs. In : Breathe, Walk and Chew - The Neural Challenge: Part I (Progress in Brain Research, Vol, 187) (Gossard JP, Dubuc R, Kolta A, Eds.) (2010)
  • Author(s): Kang Y, Saito M, Toyoda H, Sato H.
  • Publisher: Elsevier, Amsterdam
• [Book] Recruitment of masseter motoneurons by spindle Ia inputs and its modulation by leak K+ channels. In: Interface Oral Health Science 2009 (Sasano T, Suzuki O, Eds.) (2010)
  • Author(s): Kang Y, Toyoda H, Saito M, Sato H
  • Publisher: Springer, Tokyo
• [Book] Breathe, Walk and Chew (2010)
  • Author(s): Kang, Y., et al.
  • Publisher: Elsevier
• [Book] Interface Oral Health Science 2009 (2010)
  • Author(s): Kang, Y., et al.
  • Publisher: Springer