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A-激酶锚定蛋白 9 和 IKs 通道调节。

A-kinase anchoring protein 9 and IKs channel regulation.

机构信息

Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

出版信息

J Cardiovasc Pharmacol. 2011 Nov;58(5):459-13. doi: 10.1097/FJC.0b013e318232c80c.

Abstract

A-kinase anchoring proteins (AKAPs) create compartmentalized environment inside the cell to bring various signaling molecules to their targets. In the heart, a slowly activating potassium channel (IKs) important for cardiac repolarization is tightly regulated by the sympathetic nervous system in an AKAP-dependent manner. IKs channel forms a macromolecular complex with AKAP9 and other enzymes, such as protein kinase A, phosphatase, adenylyl cyclase, and phosphodiesterase, all of which are responsible to control the phosphorylation state of the channel. Such a complex thus ensures the IKs channel to be regulated properly to maintain the normal cardiac rhythm. Disruptions of various elements of the complex have been found to cause severe pathological consequences, including the long QT syndrome.

摘要

锚定蛋白激酶 A 激酶锚定蛋白 (AKAPs) 在细胞内创建分隔环境,将各种信号分子带到其靶标处。在心脏中,一种对心脏复极化很重要的缓慢激活钾通道 (IKs) 受交感神经系统以 AKAP 依赖性方式进行严格调节。IKs 通道与 AKAP9 和其他酶(如蛋白激酶 A、磷酸酶、腺苷酸环化酶和磷酸二酯酶)形成一个大分子复合物,所有这些酶都负责控制通道的磷酸化状态。因此,这样的复合物可确保 IKs 通道得到适当调节,以维持正常的心脏节律。已经发现该复合物的各种成分的破坏会导致严重的病理后果,包括长 QT 综合征。

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