The Na+/Ca2+ exchanger protein was first isolated from cardiac sarcolemma in 1988 and cloned in 1990. This allowed study of Na+/Ca2+ exchange at the molecular level to begin. I will review the story leading to the cloning of NCX and the research that resulted from this event. This will include structure-function studies such as determination of the numbers of transmembrane segments and topological arrangement. Information on ion transport sites has been gathered from site-directed mutagenesis. The regions involved in Ca2+ regulation have been identified, analyzed, and crystallized.We have also generated genetically altered mice to study the role of NCX in the myocardium. Of special interest are mice with atrial- or ventricular-specific KO of NCX that reveal new information on the role of NCX in excitation-contraction coupling and in cardiac pacemaker activity.
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机译:Na + sup> / Ca 2 + sup>交换蛋白于1988年首次从心脏肌膜分离出来,并于1990年克隆。这使得可以研究Na + sup> / Ca 2 + sup>在分子水平上开始交换。我将回顾导致NCX克隆的故事以及此事件引起的研究。这将包括结构功能研究,例如确定跨膜片段的数目和拓扑结构。有关离子迁移位点的信息已从定点诱变中收集。已经确定,分析和结晶了参与Ca 2 + sup>调控的区域。我们还产生了转基因小鼠,以研究NCX在心肌中的作用。特别感兴趣的是具有NCX的心房或心室特异性KO的小鼠,这些小鼠揭示了有关NCX在兴奋收缩耦合和心脏起搏器活动中的作用的新信息。
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