| Project/Area Number |
15300134
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Nagoya University |
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Principal Investigator |
NAKAYAMA Shinsuke Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (30192230)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Yasushi Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (80303650)
INOUE Soichiro Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (20324428)
MATSUBARA Tatsuaki Aichi-Gakuin University, School of Dentistry, Professor, 歯学部, 教授 (30209598)
SUZUKI Hikaru Nagoya City University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (80037548)
TAKAKI Miyako Nara Medical University, School of Medicine, Professor, 医学部, 教授 (00033358)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2003: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | autonomic nervous system / pacemaker / c-Kit-immunopositive interstitial cells / Ca oscillations |
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| Research Abstract |
It has recently been suggested that not only the heart, pacemaker cells play an important role in generating spontaneous rhythmicity of the tissues and organs containing smooth muscle [e.g. gastrointestinal (GI) tracts, urinary bladder, lymph ducts, etc.], and that autonomic nervous system organizes their activity. During the tenure of the research grant (2003.4-2006.3), we investigated mechanisms underlying the spontaneous rhythmicity.
First, we have revealed that revealed that co-ordinate actions of intracellular Ca^<2+> release channels, such as ryanodine receptors (RyR) and InsP_3 receptors (InsP_3R), yield pacemaker [Ca^<2+>]_i oscillations, in support with Ca^<2+> influx from the extracellular space [presumably due to transient receptor potential-like (TRP) non-selective cation channels]. Especially, our study has provided the first evidence for the involvement of RyR in pacemaker [Ca^<2+>]_i oscillations of stomach, small intestine, and gut-like organ formed from embryonic stem (
… More
ES) cells.
Very recently, a Korean group has reported that Melastatin-type TRP channel 7 (TRPM7) plays an essental role in ICC pacemaking. Interestingly, this non-selective cation channel presumably corresponds to Na^+ -independent Mg^<2+> influx that we had demonstrated using nuclear magnetic resonance.
Our experiments also have suggested that special purinoceptors (P2X_2 and P2X_5) and ATP-sensitive K channels (K_<ATP>) associated with pancreatic-type sulphonylurea receptors provide important modulation on ICC pacemaker [Ca^<2+>]_i oscillations. Furthermore, we have revealed that some ion channels essential for pacemaker [Ca^<2+1>]i oscillations are preserved in GIST (gastrointestinal stromal tumuor) cells.
Lastly, I would like to mention about experiments in detrusor smooth muscle cells. Detrusor cells show spontaneous electrical currents during muscarinic receptor stimulation. Actually, the results on this spontaneous activity have greatly helped in planning experiments to investigate ICC pacemaker activity. Less
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