Mechanisms of antiarrhythmic drugs via gene expression

抗心律失常药物通过基因表达的机制

• 批准号: 05670604
• 负责人: KAMIYA Kaichiro
• 金额: $ 1.34万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670604/
• 关键词: Amiodarone; ion channels; action potential; Kv1.5 channels; mRNA

In the present study, we examined chronic effects of amiodarone(AM) on action potentials and ionic currents of rabbit and rat ventricular myocytes and Kv1.5, a Shaker-like delayd rectifier K^+ channel. In single ventricular myocytes of rabbits treated with amiodarone 100 mg/Kg/day for 4 weeks, action potential duration (APD) was prolonged. Chronic amiodarone demonstrated decreased in current densities of ICa, IK and Ito. Northern blot analysis showed that levels of Kv1.5 mRNA were decreases in amiodarone treated rat myocytes compared with non treated myocytes. These results suggest that 1)acute and chronic amiodarone exerts divergent effects on action potential configuration and ionic currents in cardiac muscle. 2)prolongation in APD by the long-term treatment of amiodarone was derived from the inhibition of Ito and IK,while shortening of APD by the perfusion of the drug was caused by the inhibition of inward currents, 3)antiarrhythmic action of chronic treatment of amiodarone may be derived by the depression of repolarizing potassium channels through modulation of potassium channels gene expression.

本研究观察了胺碘酮（amiodarone，AM）对家兔和大鼠心室肌细胞动作电位、离子电流和Kv 1.5通道的慢性作用。胺碘酮100 mg/Kg/d给药4周，可使家兔单个心室肌细胞动作电位时程（APD）延长。慢性胺碘酮可降低伊卡、IK和Ito的电流密度。北方印迹分析显示胺碘酮处理的大鼠心肌细胞Kv 1.5 mRNA水平较未处理的心肌细胞降低。结果提示：1）急性和慢性胺碘酮对心肌动作电位构型和离子电流的影响不同。2)胺碘酮延长动作电位时程是由于抑制Ito和IK，而缩短动作电位时程是由于抑制内向电流。3）胺碘酮的抗心律失常作用可能是通过调节钾通道基因表达抑制复极钾通道。

项目成果

TOYAMA Junji: "Ca2+calmodulin mediated modulation of the electrical coupling of ventriclar myocytes isolated from guinea pig heart." Journal of Molecular and Cellular Cardiology. 26. 1007-1015 (1994)

TOYAMA Junji：“Ca2 钙调蛋白介导从豚鼠心脏中分离出的心室肌细胞的电耦合调节。”

神谷香一郎,外山淳治: "不整脈 杉本恒明,矢崎義雄,泰江弘文(編)(ハンディ版)" 中山書店, 455 (1993)

神谷浩一郎、富山润二：“心律失常杉本常明、矢崎义夫、安江博文（编）（方便版）”中山书店，455（1993）

神谷香一郎: "Amiodarne急性投与が家兎単離心室細胞に及ぼす電気生理学的作用" 名古屋大学環境医学研究所年報. 44. 230-232 (1993)

Koichiro Kamiya：“急性施用胺碘酮对离体兔心室细胞的电生理影响”名古屋大学环境医学研究所年度报告 44. 230-232 (1993)。

神谷香一郎: "家兎心筋K電流に対するamiodaroneの急性及び慢性作用の比較" 名古屋大学環境医学研究所年報. 45. 172-174 (1994)

Koichiro Kamiya：“胺碘酮对兔子心肌 K 电流的急性和慢性影响的比较”名古屋大学环境医学研究所年度报告 45. 172-174 (1994)。

KAMIYA Kaichiro: "Acute and chronic effects of amiodarone on the repolarizing currents of single rabbit ventricular myocytes." Environmental Medicine. 38. 155-158 (1994)

KAMIYA Kaichiro：“胺碘酮对单个兔心室肌细胞复极电流的急性和慢性影响。”