Yamanushi T T, Shui Z, Leach R N, Dobrzynski H, Claydon T W, Boyett M R
Cardiovascular Research Group, School of Medicine, University of Manchester, Manchester, United Kingdom.
Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H1737-46. doi: 10.1152/ajpheart.01287.2005. Epub 2006 Sep 29.
In the heart, ACh activates the ACh-activated K(+) current (I(K,ACh)) via the M(2) muscarinic receptor. The relationship between desensitization of I(K,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,ACh) declined by approximately 62% with time constants of 1.5 and 26.9 min, whereas approximately 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,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,ACh) desensitization.
在心脏中，乙酰胆碱（ACh）通过M2毒蕈碱受体激活乙酰胆碱激活的钾电流（I(K,ACh)）。I(K,ACh)脱敏与M2受体内化之间的关系已在大鼠心房细胞中进行了研究。应用稳定的毒蕈碱激动剂卡巴胆碱2小时，I(K,ACh)随时间下降约62%，时间常数分别为1.5分钟和26.9分钟，而约83%的M2受体从细胞膜内化，时间常数分别为2.9分钟和51.6分钟。用β-肾上腺素能受体激酶1（G蛋白偶联受体激酶2）和β-抑制蛋白2转染细胞，在激动剂作用3分钟期间，显著增加了I(K,ACh)脱敏和M2受体内化。暴露于卡巴胆碱2小时的细胞中内化的M2受体与网格蛋白共定位，而不与小窝蛋白共定位。得出的结论是，M2受体通过G蛋白偶联受体激酶2和β-抑制蛋白2依赖性内化进入网格蛋白包被的囊泡可能在I(K,ACh)脱敏中起主要作用。
