2001 Fiscal Year Final Research Report Summary
DO CYSTEINES LOCATED NEAR THE CHANNEL PORE OF THE RYANODINE RECEPTOR FUNCTION AS TARGET AMINO ACID FOR REACTIVE OXYGEN SPECIES?
| Project/Area Number |
12670044
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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 |
General physiology
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| Research Institution | NAGOYA GITY UNIVERSITY |
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Principal Investigator |
OBA Toshiharu NAGOYACITY UNIVERSITY, MEDICAL SCHOOL, ASSOCIATE PROFESSOR, 医学部, 助教授 (50008330)
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| Co-Investigator(Kenkyū-buntansha) |
MURAYAMA Takashi NAGOYACITY UNIVERSITY, MEDICAL SCHOOL, ASSISTANT PROFESSOR, 医学部, 講師 (10230012)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Ryanodine receptor / single channel current / cysteine residue / redox potential / 活性酸素 |
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| Research Abstract |
Excitation-contraction (E-C) coupling is the process whereby sarcolemmal depolarization is translated into muscle contraction. This signal transmission process occurs at the triad junction, where the sarcoplasmic reticulum (SR) abuts the transverse tubule. The molecular bases of E-C coupling involves the interaction between two proteins, the SR Ca^<2+>-release channel/ryanodine receptor (RyR) and L-type Ca^<2+> channel/DHP receptor (voltage sensor) in transverse tubules. The mechanism underlying the signal transmission from DHPR to RyR remains unknown. We have identified two classes of ryanodine receptor trpe1 (RyR1) channel with distinct open probabilities (termed high-Po and low-Po) upon exposure to Ca^<2+> concentrations in rabbit skeletal muscle. Effects of redox reagents and channels. The channel conductance and mean open time were similar between channels. Addition of DTT converted the high-Po channel to a state similar to the intact low-Po channel. The high-Po channel responded to caffeine and adenine nucleotides. The low-Po channel was activated by exposure to an oxidant, pCMPS, dose-dependently. Dependence of the oxidized low-Po channel to Ca^<2+> and adenine nucleotide was similar to that of the intact high-Po channel. The low-Po channel was insensitive to caffeine or adenine nucleotide, but could still response to pCMPS. Shift of channel responsiveness from low-Po to high-Po state, and vice versa, was also induced by cis redox potential. These results suggest that cis redox states of the channel alter the response to some channel activators such as Ca^<2+>, caffeine and adenine nucleotides, as well as the channel gating.
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