1997 Fiscal Year Final Research Report Summary
ACh recognition and modulation of the inhibitory nicotinic ACh receptor
| Project/Area Number |
08680723
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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 |
Biophysics
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| Research Institution | KOBE UNIVERSITY |
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Principal Investigator |
NAGAHAMA Tatsumi FACULTY OF SCIENCE,KOBE UNIVERSITY,ASSOCIATE PEOFESSOR, 理学部, 助教授 (70145001)
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| Project Period (FY) |
1996 – 1997
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| Keywords | inhibitory ACh receptor / Cl^- channel / Lophotoxin / Bippinatin / nicotinic receptor / ACh binding site / Aplysia / IJP |
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| Research Abstract |
Firing of Aplysia cholinergic MA neurons produces IPSPs in the jaw-closing (JC) motor neurons and IJPs in the JC muscle fibers. We previously demonstrated that the ACh receptors producing these inhibitory responses may be nicotinic, and the muscle receptors may be associated with Cl^- channel. Lophotoxin and the three analogues (bippinatin-A,B,C)are known to react covalently with Tyr^<190> in the ACh binding site of the receptor and inhibit the function. Bimolecular reaction constants decreased in the order bippinatin-B>A>C for the ACh binding site. In the present study the effects of these analogues on the IJPs or IPSPs were explored and compared with those on the excitatory responses to know the ACh recognition of the inhibitory ACh receptors. Bippinatin-B largely reduced the size of the IJPs, while bippinatin-A and -C increased it. The voltage clamp experiments of the JC neurons showed that the reversal potential of the synaptic current response was shifted toward more positive when the Cl^- was imjected into the JC neurons, suggesting that the ACh receptor in the JC neurons also may be associated with Cl^- channel. Bippinatin-B largely reduced the size of the IPSPs while bippinatin-A initially increased it (ca.25%) and reduced it later. The effect of bippinatin-C was more complex. Initially bippinatin-C largely increased the IPSP size (ca.200%) and then reduced it. After that the MA firing tended to produce the large depolarizing response and finally all responses ceased. These results suggest that the ACh binding site of the inhibitory receptor may be similar to that of the excitatory ACh receptor but the fine molecular structure around the binding site may be different between them.
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Research Products
(15 results)
