| Project/Area Number |
17591937
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
FUNAHASHI Makoto Hokkaido Univ., Grad. School of Dent. Med., Asso. Prof., 大学院歯学研究科, 助教授 (80221555)
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| Co-Investigator(Kenkyū-buntansha) |
SOGAWA Chiharu Okayama Univ., Grad.School of Med.Dent.& Pharmaceut.Sci., Assistant, 大学院医歯薬学総合研究科, 助手 (10253022)
MITOH Yoshihiro Okayama Univ., Grad. School of Med.Dent.& Pharmaceut.Sci., Assistant, 大学院医歯薬学総合研究科, 助手 (20240872)
SOGAWA Norio Okayama Univ., Grad.School of Med.Dent.& Pharmaceut.Sci., Assistant, 大学院医歯薬学総合研究科, 助手 (30236153)
MATSUO Ryuji Okayama Univ., Grad.School of Med.Dent.& Pharmaceut. Sci., Prof., 大学院医歯薬学総合研究科, 教授 (30157268)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | area postrema / brain slice / hyperpolarization-activated cation current / patch-clamp method / rat |
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| Research Abstract |
We performed whole-cell patch-clamp recordings from area postrema neurons to investigate the functional and biological roles of the hyperpolarization-activated cation current (Ih).
1) Morphological properties
Using electrophysiological criteria, AP neurons were subdivided into three groups : 1) cells displaying both the hyperpolarization-activated cation current (I_h) and the fast transient outward current (fast I_<to>) ; 2) cells displaying only the fast I_<to> ; and 3) cells displaying only the slow Ito. All AP neurons had a single axon that was distinctly thinner than the cells' dendrites. No systematic differences, across groups, in the orientation of dendrites or axons were identified. Mean values of cell size and capacitance of neurons from group 3 were significantly larger than those of the other groups. Interestingly, a number of cells from group 1 and 3 but not group 2 were found to extend their dendrites into the nucleus tractus solitarius (NTS), suggesting that AP neurons coul
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d receive vagal afferent inputs at their dendritic termini within the NTS. Although the AP have been implicated to contain uniformly shaped neurons, this study indicates the presence of significantly different subpopulations of AP neurons, which were characterized not only electrophysiologically but also morphologically.
2) Sensitivity to ATP
Most area postrema neurons responded to ATP application, and most responses were excitatory. Voltage-clamp recordings showed three different types of response : 1) a postsynaptic or extrasynaptic excitatory response (inward currents ; n=26/51 cells), 2) a presynaptic excitatory response (increased frequency of miniature excitatory postsynaptic currents with only a small direct postsynaptic current; n=24/51 cells, or 3) a postsynaptic inhibitory response (outward current ; n=1/51). The excitatory responses were found in both of the two major electrophysiological cell classes, i.e. cells displaying I_h and cells not displaying I_h, while the inhibitory responses were found in only cells not displaying I_h. Current-clamp recordings showed ATP-induced depolarization (n=13/15) or hyperpolarization (n=2/15) of membrane potential that modulated the frequency of action potentials. In the presence of CNQX, mEPSCs were abolished and bath applied ATP did not generate mEPSCs, indicating that glutamate release was facilitated by the activation of presynaptically located ATP receptors. Our pharmacological results from studies with ATP, aβme-ATP, βyme-ATP and PPADS indicate that P2X_2, P2X_5 and P2X_7 are the most likely subunits which compose the P2X receptor in the post-and/or extrasynaptic regions. We conclude that half of the presynaptic P2X receptors are most likely composed of P2X_2, P2X_5 and P2X_7 subunits while the others also contain P2X_1 subunits. It is well known that P2X_7 subunit forms only homomultimeric P2X receptors. Finally, the present study suggests that purinoceptor activation may contribute to the control of several autonomic functions by area postrema neurons. Less
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