title: Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in motor learning and memory.
abstract: Plasma membrane Na+/Ca2+-exchangers play a predominant role in Ca2+ extrusion in brain. Neurons express several different Na+/Ca2+-exchangers belonging to both the K+-independent NCX family and the K+-dependent NCKX family. The unique contributions of each of these proteins to neuronal Ca2+ homeostasis and/or physiology remain largely unexplored. To address this question, we generated mice in which the gene encoding the abundant neuronal K+ -dependent Na+/Ca2+-exchanger protein, NCKX2, was knocked out. Analysis of these animals revealed a significant reduction in Ca2+ flux in cortical neurons, a profound loss of long term potentiation and an increase in long term depression at hippocampal Schaffer/CA1 synapses, and clear deficits in specific tests of motor learning and spatial working memory. Surprisingly, there was no obvious loss of photoreceptor function in cones, where expression of the NCKX2 protein had been reported previously. These data emphasize the critical and non-redundant role of NCKX2 in the local control of neuronal [Ca2+] that is essential for the development of synaptic plasticity associated with learning and memory.
authors.affiliation: The Hotchkiss Brain Institute, Libin Cardiovascular Institute of Alberta, Canada.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Li
authors.forename: Lech
authors.initials: L
authors.lastname: Kiedrowski
authors.forename: François
authors.initials: F
authors.lastname: Tremblay
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Fernandez
authors.forename: Marco
authors.initials: M
authors.lastname: Perizzolo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Winkfein
authors.forename: Ray W
authors.initials: RW
authors.lastname: Turner
authors.forename: Jaideep S
authors.initials: JS
authors.lastname: Bains
authors.forename: Derrick E
authors.initials: DE
authors.lastname: Rancourt
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lytton
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D006624:Hippocampus / Q000502:physiology; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: C491739:Slc8a2 protein, mouse; D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger; D002118:Calcium