ATRIAL G-PROTEIN-ACTIVATED K+-CHANNEL - EXPRESSION CLONING AND MOLECULAR-PROPERTIES
ATRIAL G-PROTEIN-ACTIVATED K+-CHANNEL - EXPRESSION CLONING AND MOLECULAR-PROPERTIES
复制标题
DOI：
10.1073/pnas.90.21.10235
复制
发表时间：
1993-11-01
影响因子：
11.1
通讯作者：
DAVIDSON, N
中科院分区：
文献类型：
--
作者：
DASCAL, N;SCHREIBMAYER, W;DAVIDSON, N
几种离子通道的活性由异源三聚体gtp结合蛋白（G蛋白）通过膜分隔的途径控制，不涉及细胞质中间体。研究最好的例子是心房中由毒蕈碱激动剂激活的K+通道，它在调节心跳中起着至关重要的作用。为了研究激活的分子机制，我们通过功能偶联从大鼠心房cDNA文库中克隆了KGA通道，并在爪蟾卵母细胞中共表达5 -羟色胺1A型受体。KGA显示了与其他内部纠偏通道序列同源的区域，以及可能控制g蛋白相互作用的独特区域。表达的KGA通道通过G蛋白被5 -羟色胺1A、毒蕈碱m2和δ阿片受体激活。KGA被切除斑块中的鸟苷5'-[γ -硫]三磷酸激活，确认通过膜分隔的途径激活，并显示出与心房细胞内源性通道相同的电导。从大鼠大脑cDNA文库中克隆出一个几乎相同的通道（KGB1），支持了类似通道在神经元抑制中起作用的假设。
Activity of several ion channels is controlled by heterotrimeric GTP-binding proteins (G proteins) via a membrane-delimited pathway that does not involve cytoplasmic intermediates. The best studied example is the K+ channel activated by muscarinic agonists in the atrium, which plays a crucial role in regulating the heartbeat. To enable studies of the molecular mechanisms of activation, this channel, denoted KGA, was cloned from a rat atrium cDNA library by functional coupling to coexpressed serotonin type 1A receptors in Xenopus oocytes. KGA displays regions of sequence homology to other inwardly rectifying channels as well as unique regions that may govern G-protein interaction. The expressed KGA channel is activated by serotonin 1A, muscarinic m2, and delta-opioid receptors via G proteins. KGA is activated by guanosine 5'-[gamma-thio]triphosphate in excised patches, confirming activation by a membrane-delimited pathway, and displays a conductance equal to that of the endogenous channel in atrial cells. The hypothesis that similar channels play a role in neuronal inhibition is supported by the cloning of a nearly identical channel (KGB1) from a rat brain cDNA library.