| Project/Area Number |
08672617
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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 |
応用薬理学・医療系薬学
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| Research Institution | Kumamoto University |
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Principal Investigator |
LAI Zhong-Fang Kumamoto University, School of Medicine, Assistant Professor, 医学部・第二薬理講座, 助手 (90244110)
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| Co-Investigator(Kenkyū-buntansha) |
NISHI Katsuhide Kumamoto University, School of Medicine, Professor, 医学部・第二薬理講座, 教授 (00040220)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Stilbene derivatives ; / DIDS ; / SITS ; / Intracellular pH ; / Intracellular chloride concentrations ; / Cardiac ischemia ; / Ionic selective microelectrodes ; / Action potentials. / スチルベン酸誘導体 / 細胞内クロライド / 心筋細胞虚血 / イオン選択性微小電極 / 心筋細胞活動電位 / DIDS / SITS / 細胞外ATP・ / 細胞内pH / モルモット |
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| Research Abstract |
We investigated the possible role of CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger on ischemia-induced intracellular acidosis in isolated guinea pig ventricular muscle by measuring intracellular pH (pHi) and intracellular chloride (aC<@D1i@>D1l) with ion-selective microelectrode techniques. Stilbene derivatives, SITS and DIDS,were used as probes to block the CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger and their effects on action potentials (APs) , pHi and aC<@D1i@>D1l in ventricular muscles subjected to simulated ischemia were examined. Simulated ischmia was produced by stopping flow of superfusing solution and preparations were covered with mineral oil. Ischemia induced a progressive decrease in the maximum upstroke rate and resting membrane potentials, and shortened action potential duration, resulting in cessation of APs. SITS (0.5mM) and DIDS (0.1mM) delayd the onset of ischemia-induced deterioration of APs and prolonged the time to cessation of APs. Ischemia induced marked intracellular acido
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sis (pHi of control : 7.023(]SY.+-。[)0.083 ; pHi at 15 min after ischemia : 6.64(]SY.+-。[)0.012, n=6), and SITS or DIDS suppressed the development of intracellular acidosis during ischemia. There were significant differences in pHi change of SITS or DIDS-treated group at 10 and 15 min after ischemia compared with that of control group (p<0.05> . Under an external CI<@D1-@>D1-free condition, the time to cessation of APs during ischemia significantly delayd, and the acidification was suppressed. Furthermore, ischemia induced a great increase in aC<@D1i@>D1l (control : 18.74(]SY.+-。[)9.28mM ; ischemia : 55.3(]SY.+-。[)6.11mM] and this increase was suppressed by the external CI<@D1-@>D1-free or by stilbene derivatives. Present results indicate that activation of CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger is involved in the development of intracellular acidosis occurring during ischemia and that manipulation of pHi and aC<@D1i@>D1l by blocking CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchange by stilbene derivatives can attenuate ischemia-induced intracellular acidosis, thereby having beneficial effects on ischemia-induced arrhythmias. Less
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