受体激酶在中国仓鼠卵巢细胞中表达的心脏毒蕈碱钾通道短期脱敏中的作用。

Role of receptor kinase in short-term desensitization of cardiac muscarinic K+ channels expressed in Chinese hamster ovary cells.

作者信息

Shui Z, Khan I A, Tsuga H, Haga T, Boyett M R

机构信息

Department of Physiology, University of Leeds, UK.

出版信息

J Physiol. 1998 Mar 1;507 ( Pt 2)(Pt 2):325-34. doi: 10.1111/j.1469-7793.1998.325bt.x.

DOI:10.1111/j.1469-7793.1998.325bt.x

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2230799/

Abstract

The cardiac muscarinic receptor-K+ channel system was reconstructed in Chinese hamster ovary (CHO) cells by transfecting the cells with the various components of the system. The activity of the muscarinic K+ channel was measured with the cell-attached configuration of the patch clamp technique. 2. In CHO cells transfected with the channel (Kir3.1/Kir3.4), receptor (hm2) and receptor kinase (GRK2), on exposure to agonist, there was a decline in channel activity as a result of desensitization, similar to that in atrial cells. 3. Whereas the desensitization was almost abolished by not transfecting with the receptor kinase or by transfecting with a mutant receptor lacking phosphorylation sites, it was only reduced (by approximately 39%) by transfecting with a mutant receptor kinase with little/kinase activity. 4. These results suggest that the receptor kinase is responsible for desensitization of the muscarinic K+ channel and that this involves phosphorylation-dependent and -independent mechanisms.

摘要

通过用该系统的各种组分转染中国仓鼠卵巢（CHO）细胞，在其中重建了心脏毒蕈碱受体 - K⁺通道系统。采用膜片钳技术的细胞贴附模式测定毒蕈碱K⁺通道的活性。2. 在转染了通道（Kir3.1/Kir3.4）、受体（hm2）和受体激酶（GRK2）的CHO细胞中，暴露于激动剂时，由于脱敏作用，通道活性下降，这与心房细胞中的情况类似。3. 若不转染受体激酶或转染缺乏磷酸化位点的突变受体，脱敏作用几乎被消除；而转染激酶活性很低的突变受体激酶时，脱敏作用仅降低（约39%）。4. 这些结果表明，受体激酶负责毒蕈碱K⁺通道的脱敏作用，且这涉及磷酸化依赖性和非依赖性机制。