کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2198529 1551155 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Purkinje cell dysfunction and delayed death in plasma membrane calcium ATPase 2-heterozygous mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Purkinje cell dysfunction and delayed death in plasma membrane calcium ATPase 2-heterozygous mice
چکیده انگلیسی

Purkinje cell (PC) dysfunction or death has been implicated in a number of disorders including ataxia, autism and multiple sclerosis. Plasma membrane calcium ATPase 2 (PMCA2), an important calcium (Ca2 +) extrusion pump that interacts with synaptic signaling complexes, is most abundantly expressed in PCs compared to other neurons. Using the PMCA2 heterozygous mouse as a model, we investigated whether a reduction in PMCA2 levels affects PC function. We focused on Ca2 + signaling and the expression of glutamate receptors which play a key role in PC function including synaptic plasticity. We found that the amplitude of depolarization and 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor (AMPAR)-mediated Ca2 + transients are significantly higher in cultured PMCA2+/− PCs than in PMCA2+/+ PCs. This is due to increased Ca2 + influx, since P/Q type voltage-gated Ca2 + channel (VGCC) expression was more pronounced in PCs and cerebella of PMCA2+/− mice and VGCC blockade prevented the elevation in amplitude. Neuronal nitric oxide synthase (nNOS) activity was higher in PMCA2+/− cerebella and inhibition of nNOS or the soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway, which mediates nitric oxide (NO) signaling, reduced the amplitude of Ca2 + transients in PMCA2+/− PCs, in vitro. In addition, there was an age-dependent decrease in metabotropic glutamate receptor 1 (mGluR1) and AMPA receptor subunit GluR2/3 transcript and protein levels at 8 weeks of age. These changes were followed by PC loss in the 20-week-old PMCA2+/− mice. Our studies highlight the importance of PMCA2 in Ca2 + signaling, glutamate receptor expression and survival of Purkinje cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 51, Issues 1–2, August 2012, Pages 22–31
نویسندگان
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