期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 292, 期 4, 页码 H1737-H1746出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01287.2005
关键词
acethylcholine-activated potassium current; acetylcholine; Kir3.1; Kir3.4; caveolin
In the heart, ACh activates the ACh-activated K+ current ( I-K,I- ACh) via the M-2 muscarinic receptor. The relationship between desensitization of I-K,I- ACh and internalization of the M-2 receptor has been studied in rat atrial cells. On application of the stable muscarinic agonist carbachol for 2 h, I-K,I- ACh declined by similar to 62% with time constants of 1.5 and 26.9 min, whereas similar to 83% of the M-2 receptor was internalized from the cell membrane with time constants of 2.9 and 51.6 min. Transfection of the cells with beta-adrenergic receptor kinase 1 ( G protein-receptor kinase 2) and beta-arrestin 2 significantly increased I-K,I- ACh desensitization and M-2 receptor internalization during a 3-min application of agonist. Internalized M-2 receptor in cells exposed to carbachol for 2 h was colocalized with clathrin and not caveolin. It is concluded that a G protein-receptor kinase 2- and beta-arrestin 2-dependent internalization of the M-2 receptor into clathrin-coated vesicles could play a major role in I-K,I- ACh desensitization.
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