20 Years from NCX Purification and Cloning: Milestones
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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.
KeywordsNa+/Ca2+ exchange Ca2+ transport Excitation-contraction coupling Ca2+ regulation Na+ transport Cardiac pacemaking
We have had many talented colleagues over the years. Some of those who participated in the experiments presented here include Drs. Xiaoyan Ren, Satoshi Matsuoka, Larry Hryshko, Dmitri Levitski, Don Hilgemann, Jeff Abramson, Christian Pott, Robert Larbig, and Sabine Groenke.
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