title: 20 years from NCX purification and cloning: milestones.
abstract: The Na(+)/Ca(2+) exchanger protein was first isolated from cardiac sarcolemma in 1988 and cloned in 1990. This allowed study of Na(+)/Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Department of Physiology and Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1760, USA.
authors.forename: Debora A
authors.initials: DA
authors.lastname: Nicoll
authors.forename: Michela
authors.initials: M
authors.lastname: Ottolia
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Goldhaber
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Philipson
mesh_terms: D000818:Animals; D000846:Anniversaries and Special Events; D001683:Biological Clocks / Q000502:physiology*; D035843:Biomedical Research / Q000266:history; D003001:Cloning, Molecular; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D017136:Ion Transport; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D012508:Sarcolemma / Q000737:chemistry / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D019831:Sodium-Calcium Exchanger