...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >The chloride-channel blocker 9-anthracenecarboxylic acid reduces the nonlinear capacitance of prestin-associated charge movement
【24h】

The chloride-channel blocker 9-anthracenecarboxylic acid reduces the nonlinear capacitance of prestin-associated charge movement

机译：氯离子通道阻滞剂9-蒽羧酸减少了与雌激素相关的电荷运动的非线性电容

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

The basis of the extraordinary sensitivity and frequency selectivity of the cochlea is a chloride-sensitive protein called prestin which can produce an electromechanical response and which resides in the basolateral plasma membrane of outer hair cells (OHCs). The compound 9-anthracenecarboxylic acid (9-AC), an inhibitor of chloride channels, has been found to reduce the electromechanical response of the cochlea and the OHC mechanical impedance. To elucidate these 9-AC effects, the functional electromechanical status of prestin was assayed by measuring the nonlinear capacitance of OHCs from the guinea-pig cochlea and of prestin-transfected human embryonic kidney 293 (HEK293) cells. Extracellular application of 9-AC caused reversible, dose-dependent and chloride-sensitive reduction in OHC nonlinear charge transfer, Q(max). Prestin-transfected cells also showed reversible reduction in Q(max). For OHCs, intracellular 9-AC application as well as reduced intracellular pH had no detectable effect on the reduction in Q(max) by extracellularly applied 9-AC. In the prestin-transfected cells, cytosolic application of 9-AC approximately halved the blocking efficacy of extracellularly applied 9-AC. OHC inside-out patches presented the whole-cell blocking characteristics. Disruption of the cytoskeleton by preventing actin polymerization with latrunculin A or by decoupling of spectrin from actin with diamide did not affect the 9-AC-evoked reduction in Q(max). We conclude that 9-AC acts on the electromechanical transducer principally by interaction with prestin rather than acting via the cytoskeleton, chloride channels or pH. The 9-AC block presents characteristics in common with salicylate, but is almost an order of magnitude faster. 9-AC provides a new tool for elucidating the molecular dynamics of prestin function.
机译：耳蜗具有非凡的敏感性和频率选择性，其基础是对氯敏感的蛋白质，称为Prestin，可产生机电响应，并位于外毛细胞（OHC）的基底外侧质膜中。已发现化合物9-蒽羧酸（9-AC）（一种氯离子通道的抑制剂）可降低耳蜗的机电响应和OHC机械阻抗。为了阐明这些9-AC效应，通过测量来自豚鼠耳蜗的OHCs和经Prestin转染的人胚胎肾293（HEK293）细胞的非线性电容来测定Prestin的功能性机电状态。 9-AC的细胞外应用导致OHC非线性电荷转移Q（max）的可逆，剂量依赖性和氯化物敏感性降低。 Prestin转染的细胞还显示Q（max）的可逆减少。对于OHC，细胞内应用9-AC以及降低细胞内pH值对细胞外应用9-AC的Q（max）降低均无可检测的影响。在经prestin转染的细胞中，胞浆施用9-AC大约会使细胞外施用9-AC的阻断功效减半。 OHC由内而外的贴片展现了全细胞阻断特性。通过阻止肌动蛋白与拉特朗库林A聚合或通过血影蛋白与肌动蛋白与二酰胺的解偶联来破坏细胞骨架，不会影响9-AC引起的Q（max）降低。我们得出的结论是9-AC主要通过与prestin相互作用而不是通过细胞骨架，氯离子通道或pH作用于机电换能器。 9-AC嵌段具有与水杨酸盐相同的特性，但快了一个数量级。 9-AC提供了一种新工具，用于阐明蛋白素功能的分子动力学。

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