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Effects of amyloid-ß peptides on voltage-gated L-type Ca(V)1.2 and Ca(V)1.3 Ca(2+) channels.

Authors: Kim, Sunoh  Rhim, Hyewhon 
Citation: Kim S and Rhim H, Mol Cells. 2011 Sep;32(3):289-94. doi: 10.1007/s10059-011-0075-x. Epub 2011 Aug 4.
Pubmed: (View Article at PubMed) PMID:21822937
DOI: Full-text: DOI:10.1007/s10059-011-0075-x

Overload of intracellular Ca(2+) has been implicated in the pathogenesis of neuronal disorders, such as Alzheimer's disease. Various mechanisms produce abnormalities in intracellular Ca(2+) homeostasis systems. L-type Ca(2+) channels have been known to be closely involved in the mechanisms underlying the neurodegenerative properties of amyloid-ß (Aß) peptides. However, most studies of L-type Ca(2+) channels in Aß-related mechanisms have been limited to Ca(V)1.2, and surprisingly little is known about the involvement of Ca(V)1.3 in Aß-induced neuronal toxicity. In the present study, we examined the expression patterns of Ca(V)1.3 after Aß(25-35) exposure for 24 h and compared them with the expression patterns of Ca(V)1.2. The expression levels of Ca(V)1.3 were not significantly changed by Aß(25-35) at both the mRNA levels and the total protein level in cultured hippocampal neurons. However, surface protein levels of Ca(V)1.3 were significantly increased by Aß(25-35), but not by Aß(35-25). We next found that acute treatment with Aß(25-35) increased Ca(V)1.3 channel activities in HEK293 cells using whole-cell patch-clamp recordings. Furthermore, using GTP pulldown and co-immunoprecipitation assays in HEK293 cell lysates, we found that amyloid precursor protein interacts with ß(3) subunits of Ca(2+) channels instead of Ca(V)1.2 or Ca(V)1.3 α(1) subunits. These results show that Aß(25-35) chronically or acutely upregulates Ca(V)1.3 in the rat hippocampal and human kidney cells (HEK293). This suggests that Ca(V)1.3 has a potential role along with Ca(V)1.2 in the pathogenesis of Alzheimer's disease.

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CRRD Object Information
CRRD ID: 13782265
Created: 2018-08-30
Species: All species
Last Modified: 2018-08-30
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.