Project/Area Number |
18592175
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Surgical dentistry
|
Research Institution | Osaka University |
Principal Investigator |
KOIZUMI Hidehiko Osaka University, Dental Hospital, Assistant Professor (10324790)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
Keywords | Brain / Neurophvsiology / Breathing / Patch-clamp |
Research Abstract |
We have investigated the medullary control mechanisms for tongue movements. In this study, we focused on respiratory hypoglossal motor activity that was regulated by respiratory pacemaker neurons. We first analyzed electrophysiological spiking properties of respiratory pacemaker neurons using patch-clamp technique in neonatal rat brainstem slice preparations in vitro and arterially perfused juvenile rat brainstem preparations in situ. We then investigated the cellular mechanisms for respiratory drive transmission from pacemaker neurons to hypoglossal motoneurons. We concluded that several Na^+, K^+, and Ca^<2+> currents such as Ca^<2+-> activated K^+ currents were responsible for repetitive spiking behavior in respiratory pacemaker neurons by affecting their membrane after-hyperpolarization, and that some subthreshold currents including persistent Na^+ (NaP) currents contributed to frequency control of rhythmical bursts in respiratory pacemaker neurons and hypoglossal motoneurons. We f
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urther demonstrated that during normal breathing inhibitory respiratory networks regulated by Cl currents rather than pacemaker excitatory networks regulated by NaP currents were critical for rhythm generation of respiratory hypoglossal activities. During hypoxia, however, respiratory rhythm generation relied on solely NaP cellular mechanisms. We also developed the computational network models for respiratory tongue movements by using the data from our electrophysiological experiments. The computational simulation studies were performed with a collaborator, Dr. Smith at the NIH in the USA. In our network models we tested the role of NaP channel on several membrane properties of respiratory pacemaker neurons and hypoglossal motoneurons. We concluded that NaP currents were critical for rhythmical burst generation in pacemaker neurons, and that the conductance of NaP channels was responsible for pattern formation of respiratory hypoglossal motor activities including burst frequency, amplitude and duration. The findings obtained in this study will provide useful information on treatments for several respiratory disorders such as sleep apnea. Less
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