Electrophysiological study of the functional structure of the Na channel.
| Project/Area Number |
61570044
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General physiology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
SEYAMA Issei Department of Physiology, School of Medicine, Hiroshima University, Prof., 医学部, 教授 (70034006)
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| Co-Investigator(Kenkyū-buntansha) |
YAKEHIRO Masuhide Deaprtment of Physiology, School of Medicine, Hiroshima University, Research Ass, 医学部, 助手 (90166489)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1988: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1987: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1986: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Na channel / Squid axon / Blocking action / Cyclic polyamine / グラヤノトキシン / Na透性 / グアニディニウム基 / 不活性化過程 / イカ巨大神経 |
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| Research Abstract |
In this series of experiments using the internal perfusion and the voltage clamp method on squid giant axon, an attempt was made to elucidate the functional structure Na channel by using the newly found biological toxins and chemicals. The experiments were categorized as follows; 1) The mechanism of block of the Na channel from the internal surface of cell membrane by cyclic-polyamine derivatives. cyclam and its analogue having the alkylguanidunium side chain (G-cyclam) have shown to block the Na channel only from the internal surface. Mode of the block is voltage- as well as time-dependent. In the case of G-cyclam, time course of the block is governed by a single exponential function. While, cyclam blocks Na channel with a double exponential function. The enhancement of blocking action occurred when [Na]_i increased from 50 to 200 mM. Two state three barrier model well explains all these blocking actions in the Na channel. from the molecular consideration of these cyclic aolyamine ana
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logues, it is reasonable to assume that alkyl guanidinium group freely moves inside the na channel, thereby attaching the negative charged site and in ture blocking the Na channel. 2) Similar finding also obtained, when two spider toxins, JSTX-3 and NSTX-3, were applied intra-cellularly. These spider toxins have a common 2,4 dihydrooxy-phenylacethyl-aspargynil-cadabelino-ptreamine. Difference in molecular structure is recognized in the terminal where JSTX-3 has gpysine and NSTX-3 arginine residues. Since NSTX-3 exerts stronger blocking action than JSTX-3 does, again freely movable terminal group having a permanent positive charge is assumed to play an important role in blocking the Na channel. 3) Externally applied grayanotoxin (GTX), Na channel modifier, appeared in the intracellu lar phase and induced much bigger depolarization in the non-perfusion of intracellular phase than in the continuous perfusion. Thus, it has been concluded that the site of action is in the intracellular phase. Less
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Report
(3 results)
Research Products
(25 results)
