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Molecules and Cells

, 32:289 | Cite as

Effects of amyloid-β peptides on voltage-gated L-type CaV1.2 and CaV1.3 Ca2+ channels

  • Sunoh Kim
  • Hyewhon RhimEmail author
Article

Abstract

Overload of intracellular Ca2+ has been implicated in the pathogenesis of neuronal disorders, such as Alzheimer’s disease. Various mechanisms produce abnormalities in intracellular Ca2+ homeostasis systems. L-type Ca2+ channels have been known to be closely involved in the mechanisms underlying the neurodegenerative properties of amyloid-β (Aβ) peptides. However, most studies of L-type Ca2+ channels in Aβ-related mechanisms have been limited to CaV1.2, and surprisingly little is known about the involvement of CaV1.3 in Aβ-induced neuronal toxicity. In the present study, we examined the expression patterns of CaV1.3 after Aβ25–35 exposure for 24 h and compared them with the expression patterns of CaV1.2. The expression levels of CaV1.3 were not significantly changed by Aβ25–35 at both the mRNA levels and the total protein level in cultured hippocampal neurons. However, surface protein levels of CaV1.3 were significantly increased by Aβ25–35, but not by Aβ35–25. We next found that acute treatment with Aβ25–35 increased CaV1.3 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 β3 subunits of Ca2+ channels instead of CaV1.2 or CaV1.3 α1 subunits. These results show that Aβ25–35 chronically or acutely upregulates CaV1.3 in the rat hippocampal and human kidney cells (HEK293). This suggests that CaV1.3 has a potential role along with CaV1.2 in the pathogenesis of Alzheimer’s disease.

Keywords

Alzheimer’s disease co-immunoprecipitation GST pulldown intracellular Ca2+ L-type Ca2+ channels 

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Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2011

Authors and Affiliations

  1. 1.Jeollanamdo Institute of Natural Resources ResearchJangheungKorea
  2. 2.Biomedical Research CenterKorea Institute of Science and TechnologySeoulKorea

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