Journal article
Abnormal cytoplasmic calcium dynamics in central neurons of a dystonia mouse model
Neuroscience letters, Vol.548, pp.61-66
08/26/2013
DOI: 10.1016/j.neulet.2013.05.047
PMID: 23748075
Abstract
•Hippocampal neurons were cultured from a knock-in mouse model of DYT1 dystonia.•Changes in cytoplasmic calcium concentration were assessed by fluorescence imaging.•Stimulus-induced transients decayed slowly in neurons of heterozygous-mutant mice.•This effect was dependent on activation of ionotropic glutamate receptors.
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 ([Ca2+]c) in cultured hippocampal neurons shows that electrical stimulation depolarizes the neurons and increases the dendritic [Ca2+]c, which then decays slowly to the pre-stimulus level. Whereas the peak amplitude of [Ca2+]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 [Ca2+]c is readout and regulator of neuronal excitability, its abnormality represents an important cellular phenotype of dystonia
Details
- Title: Subtitle
- Abnormal cytoplasmic calcium dynamics in central neurons of a dystonia mouse model
- Creators
- Sadahiro IwabuchiYasuhiro KakazuJin-Young KohN. Charles Harata
- Resource Type
- Journal article
- Publication Details
- Neuroscience letters, Vol.548, pp.61-66
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/j.neulet.2013.05.047
- PMID
- 23748075
- ISSN
- 0304-3940
- eISSN
- 1872-7972
- Language
- English
- Date published
- 08/26/2013
- Academic Unit
- Molecular Physiology and Biophysics; Otolaryngology
- Record Identifier
- 9984025428502771
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