1998 Fiscal Year Final Research Report Summary
Mechanisms on the reperfusion arrythmias and the protection from reperfusion arrythmias : Redox reguration of the cardiac ion channels
| Project/Area Number |
09670720
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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 |
Circulatory organs internal medicine
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| Research Institution | Tottori University Faculty of Medicine |
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Principal Investigator |
HISATOME Ichiro Tottori University, The 1st Department of Medicine, Associate Professor, 医学部, 助教授 (60211504)
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| Co-Investigator(Kenkyū-buntansha) |
SUGA Masamitsu Tottori University, The 1st Department of Medicine, Clinical Fellow., 医学部附属病院, 医員
ADACHI Masamitsu Tottori University, The 1st Department of Medicine, Clinical Fellow., 医学部附属病院, 医員
TANAKA Yasunori Tottori University, Department of Physiology, Research Associate., 医学部, 助手 (60294310)
OHTAHARA Akira Tottori University, The 1st Department of Medicine, Clinical Fellow., 医学部附属病院, 医員
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| Project Period (FY) |
1997 – 1998
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| Keywords | reperfusion injury / Na channel alpha subunit / p-loop region / cysteine 373 / hH1 / hskm1 |
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| Research Abstract |
To elucidate the mechanism on the reperfusion arrythmias, we focused on the role of oxidative stress on the cardiac ion channel. We studied the effects of sulfyhydryl oxidative agents on the expressed Na channel alpha subuit of heart (hH1) or skeletal muscle (hskm1) of the cultured COS7 cells using patch clamp techniques. 1) Effects of sulfhydyl oxidative agents on hskm1 : HgCI2 depressed hH1 in dose-depedent manner, although either thimerosal or DTDP could not affect hskm1. Either pretreatment or post treatment with DTT could protect hskm1 from inhibition by HgCl2.2) Comparison of the sensitivity of hH1 to sulfhydryl oxidative agents with that of hskm1. : The Kd of HgCl2 for inhibition of hH1 was significantly lower than that for inhibition of hskm1. According to the amino sequences of the pore forming region of the Na channel a subuit, the cysteine of the P loop region in the domain 1 was existing in hill not in hskm1.3) The role of the cysteine 373 in the p loop region of the domain 1. : To elucidate the mechansm on the higher sensitivity of hill to HgCl2, we introduced the point mutation substituting tyrosine 373 for cysteien 373 in hill and studied the effect of HgCl2 on mutant hHl. This mutant acquired the resistance against HgCl2. These results suggest that oxidative stress block Na channel via forming the disulfide bond among the cysteine residues and cysteine 373 played the povotal role for the heart specific sensitivity to oxidaitve stress.
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[Publications] Yasunori Tanaka, Ichiro Hisatome, Jiro Miyamoto, Tadashi Urashima, Kaoru Ikeda, Yumi Yamanouchi, Norihito Sasaki, Toru Kinugawa, Kazuhide Ogino, Osamu Igawa, Akio Yoshida, Chiaki Shigemasa, Yasutaka Kurata, and Ryoichi Sato.: "Enhancing effects of salicylate on tonic and phasic block of Na+ channels by class 1 antiarrhythmic agents in the guinea pig papillary and ventricular myocytes." Biochimica et Biophysica Acta. (in press). (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yasunori Tanaka, Ichiro Hisatome, Norihito Sasaki, Gias U Ahmed, Toru Yatsuhashi, Yumi Yamanouchi, Toshihiko Uchida, Toshihiro Hamada, Shin-ichi Taniguchi, Kazuhide Ogino, Osamu Igawa, Akio Yoshida1 Chiaki Shigemasa, Ryoichi Sato.: "Mechanism of Inhibition of the Sodium Current by Tocainide in Guinea-pig Isolated Ventricular Cells." Gen.Pharmacol.(in press). (1999)
Description
「研究成果報告書概要(欧文)」より
