title: Abnormal cytoplasmic calcium dynamics in central neurons of a dystonia mouse model.
abstract: Increased activities of cytoplasmic calcium and the excitatory neurotransmitter glutamate have been independently implicated in dystonia pathophysiology. However, cellular-level evidence linking these two features is not available. Here we show that glutamate-dependent changes in neuronal calcium dynamics occur in a knock-in mouse model of DYT1 dystonia, the most common hereditary form of this disorder. Fluorescence-based analysis of the dynamics of cytoplasmic calcium concentration ([Ca(2+)]c) in cultured hippocampal neurons shows that electrical stimulation depolarizes the neurons and increases the dendritic [Ca(2+)]c, which then decays slowly to the pre-stimulus level. Whereas the peak amplitude of [Ca(2+)]c was not affected, the decay period was prolonged in neurons of heterozygous mice whose genotype reflects the human condition. We found that this effect was blocked by the antagonists of ionotropic glutamate receptors, and confirmed that glutamate receptors are present in these neurons. As the [Ca(2+)]c is readout and regulator of neuronal excitability, its abnormality represents an important cellular phenotype of dystonia.
authors.affiliation: Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Iwabuchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kakazu
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Koh
authors.forename: N Charles
authors.initials: NC
authors.lastname: Harata
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D004421:Dystonia / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*
chemical_list: D017470:Receptors, Glutamate; D002118:Calcium
keywords: Calcium-sensitive dye; DYT1 dystonia; Fluorescence imaging; Glutamate receptor; Neuron