• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Rapid desensitization of G protein-gated inwardly rectifying K(+) currents is determined by G protein cycle.
【24h】

Rapid desensitization of G protein-gated inwardly rectifying K(+) currents is determined by G protein cycle.

机译：通过G蛋白循环确定G蛋白门控的内向整流K（+）电流的快速脱敏。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Activation of G protein-gated inwardly rectifying K(+) (GIRK) channels, found in the brain, heart, and endocrine tissue, leads to membrane hyperpolarization that generates neuronal inhibitory postsynaptic potentials, slows the heart rate, and inhibits hormone release. During stimulation of G(i/o)-coupled receptors and subsequent channel activation, it has been observed that the current desensitizes. In this study we examined mechanisms underlying fast desensitization of cloned heteromeric neuronal Kir3.1+3.2A and atrial Kir3.1+3.4 channels and also homomeric Kir3.0 currents in response to stimulation of several G(i/o) G protein-coupled receptors (GPCRs) expressed in HEK-293 cells (adenosine A(1), adrenergic alpha(2A), dopamine D(2S), M(4) muscarinic, and GABA(B1b/2) receptors). We found that all agonist-induced currents displayed a similar degree of desensitization except the adenosine A(1) receptor, which exhibits an additional desensitizing component. Using the nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), we found that this is due to a receptor-dependent, G protein-independent process. Using Ca(2+) imaging we showed that desensitization is unlikely to be accounted for solely by phospholipase C activation and phosphatidylinositol 4,5-bisphosphate (PIP(2)) hydrolysis. We examined the contribution of the G protein cycle and found the following. First, agonist concentration is strongly correlated with degree of desensitization. Second, competitive inhibition of GDP/GTP exchange by using nonhydrolyzable guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS) has two effects, a slowing of channel activation and an attenuation of the fast desensitization phenomenon. Finally, using specific Galpha subunits we showed that ternary complexes with fast activation rates display more prominent desensitization than those with slower activation kinetics. Together our data suggest that fast desensitization of GIRK currents is accounted for by the fundamental properties of the G protein cycle.
机译：在大脑，心脏和内分泌组织中发现的G蛋白门控的内向整流性K（+）（GIRK）通道的激活导致膜超极化，产生神经元抑制突触后突触电位，减慢心律并抑制激素释放。在刺激G（i / o）耦合的受体和随后的通道激活过程中，已观察到电流降低了灵敏度。在这项研究中，我们研究了克隆的异聚神经元Kir3.1 + 3.2A和心房Kir3.1 + 3.4通道快速脱敏的基础机制，以及响应几个G（i / o）G蛋白偶联刺激的同质Kir3.0电流的机制。受体（GPCR）在HEK-293细胞中表达（腺苷A（1），肾上腺素α（2A），多巴胺D（2S），M（4）毒蕈碱和GABA（B1b / 2）受体）。我们发现，除腺苷A（1）受体外，所有激动剂诱导的电流均表现出相似的脱敏程度，而腺苷A（1）受体则具有额外的脱敏成分。使用不可水解的GTP类似物鸟苷5'-O-（3-硫代三磷酸）（GTPgammaS），我们发现这是由于受体依赖性，G蛋白依赖性过程。使用Ca（2+）成像，我们表明脱敏不太可能仅由磷脂酶C激活和磷脂酰肌醇4,5-二磷酸（PIP（2））水解引起。我们检查了G蛋白循环的贡献，发现了以下内容。首先，激动剂浓度与脱敏程度密切相关。第二，通过使用不可水解的鸟苷5'-O-（2-硫代二磷酸）（GDPbetaS）竞争性抑制GDP / GTP交换具有两个作用，通道激活的减慢和快速脱敏现象的减弱。最后，使用特定的Galpha亚基，我们显示出活化速度快的三元复合物比活化动力学慢的三元复合物表现出更突出的脱敏作用。我们的数据一起表明，GIRK电流的快速脱敏是由G蛋白循环的基本特性引起的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号