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EFFECTS OF CARDIAC DRUGS ON SODIUM-CALCIUM EXCHANGER

EFFECTS OF CARDIAC DRUGS ON SODIUM-CALCIUM EXCHANGER
强心药对钠钙交换体的影响
批准号:
09670098
负责人:
KIMURA Junko
金额:
$2.05万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1998

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项目成果

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中文摘要
翻译
(1)KB-R7943is a drug we first reported to inhibit Na-Ca exchange current(INCX)with IC I D 250 ii D2 0.3µM for outward iNCX and with 17µM for inward iNCX when one directional iNCX flows.However,under an experimental condition where bi-directional iNCX flows.The drug inhibits both outward and inward iNCX equipotently.This result can be explained by different conformation between the binding forms for external Na and Ca.(2)A new cardioprotective drug,JTV-519 inhibited Na-,Ca-,and inwardly rectifying K-currents in guinea pig cardiac ventricular cells。The block of Na current,was voltage-and use-dependent and was similar to quinidine rather than to lidocaine。IC I D 250 I D 2 for Na-current was 2µM at-90 mV and 1.2µM at-60 mV。The drug shortened the plateau of the action potential.(3)Butanedione monoxime(BDM)inhibited iNCX in guinea pig ventricular cells。IC D 250个D 2 value was 2.4 mM.A similar drug,pralidoxime also inhibited iNCX,indicating that dephosphorylation of the exchanger may be a reason.We are currently investigating mutated NCX for the mechanism of the drug action.(4)Class III antiarrhythmic drug,amiodarone inhibits iNCX.IC I D 250个D 2 was 3µM.Trypsin in the pipette solution diminished the inhibitory effect of amiodarone,indicating that the drug affects internal side of the exchanger.(5)Anti-diabetic drug,troglitazone inhibited L-type Ca current in guinea pig ventricular cells.The effect was voltage-dependent。IC I D 250个D 2 values were 0.8µM at a holding potential of-50 mV and larger than 10µM at-80 mV。
英文摘要
(1) KB-R7943 is a drug we first reported to inhibit Na-Ca exchange current (iNCX) with ICィイD250ィエD2 0.3 μM for outward iNCX and with 17μM for inward iNCX when one directional iNCX flows. However, under an experimental condition where bi-directional iNCX flows. The drug inhibits both outward and inward iNCX equipotently. This result can be explained by different conformation between the binding forms for external Na and Ca.(2) A new cardioprotective drug, JTV-519 inhibited Na-, Ca-, and inwardly rectifying K-currents in guinea pig cardiac ventricular cells. The block of Na current, was voltage- and use-dependent and was similar to quinidine rather than to lidocaine. ICィイD250ィエD2 for Na-current was 2 μM at -90 mV and 1.2 μM at -60 mV. The drug shortened the plateau of the action potential.(3) Butanedione monoxime (BDM) inhibited iNCX in guinea pig ventricular cells. ICィイD250ィエD2 value was 2.4 mM. A similar drug, pralidoxime also inhibited iNCX, indicating that dephosphorylation of the exchanger may be a reason. We are currently investigating mutated NCX for the mechanism of the drug action.(4) Class III antiarrhythmic drug, amiodarone inhibits iNCX. ICィイD250ィエD2 was 3 μM. Trypsin in the pipette solution diminished the inhibitory effect of amiodarone, indicating that the drug affects internal side of the exchanger.(5) Anti-diabetic drug, troglitazone inhibited L-type Ca current in guinea pig ventricular cells. The effect was voltage-dependent. ICィイD250ィエD2 values were 0.8 μM at a holding potential of -50 mV and larger than 10 μM at -80 mV.
期刊论文(0)
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会议论文
Watano, T.: "Calcium-dependent inhibition of the soudium-calcium exchange current by KB-R7943" Canadian Journal of Cardiology. 14. 259-262 (1998)
Watano, T.:“KB-R7943 对钠-钙交换电流的钙依赖性抑制”加拿大心脏病学杂志。
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通讯作者:
Watano T.,Kimura J.: "Calcium-dependent inhibition of the sodium-calcium excharge current by KBR-7943" Canadian J.Cardiol.14(in press). (1998)
Watano T.,Kimura J.:“KBR-7943 对钠钙放电电流的钙依赖性抑制”Canadian J.Cardiol.14(印刷中)。
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Kimura J.: "第11回国際女性技術者・科学者会議医療部門分科会記念医学論集"第11回国際女性技術者・科学者会議医療部門分科会. 162-165 (1999)
Kimura J.:“第 11 届国际女工程师和科学家会议医学部纪念医学论文集”第 11 届女工程师和科学家国际会议医学部 162-165 (1999)。
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