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新型 I 类抗心律失常药物 AN-132 可抑制乙酰胆碱诱导的心房肌细胞钾电流。

AN-132, a new class I anti-arrhythmic agent, depresses the acetylcholine-induced K+ current in atrial myocytes.

作者信息

Kurachi Y, Nakajima T, Ito H, Sugimoto T

机构信息

2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.

出版信息

Eur J Pharmacol. 1989 Jun 20;165(2-3):319-22. doi: 10.1016/0014-2999(89)90729-2.

Abstract

AN-132, a newly developed anti-arrhythmic agent, effectively depressed the acetylcholine (ACh)-induced K+ current (IK.ACh), as measured with the tight-seal, whole-cell clamp technique in single atrial cells of guinea-pig. When GTP-gamma S was loaded into the cell through a pipette, IK.ACh was activated persistently, probably due to irreversible activation of G proteins by GTP-gamma S. AN-132 was much less potent to depress IK.ACh in GTP-gamma S-loaded cells than in GTP-loaded cells. In conclusion, AN-132 may block mainly the cardiac muscarinic ACh receptors to suppress IK.ACh.

摘要

AN - 132是一种新研发的抗心律失常药物,在豚鼠单个心房细胞中,采用紧密密封全细胞膜片钳技术测量发现,它能有效抑制乙酰胆碱(ACh)诱导的钾电流(IK.ACh)。当通过移液管将GTP - γ S导入细胞时,IK.ACh被持续激活,这可能是由于GTP - γ S对G蛋白的不可逆激活所致。与导入GTP的细胞相比,AN - 132对导入GTP - γ S的细胞中IK.ACh的抑制作用要弱得多。总之,AN - 132可能主要通过阻断心脏毒蕈碱型ACh受体来抑制IK.ACh。

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