|
KMID : 0578320110320030289
|
|
Molecules and Cells
2011 Volume.32 No. 3 p.289 ~ p.294
|
|
|
Effects of Amyloid-β Peptides on Voltage-Gated L-Type CaV1.2 and CaV1.3 Ca2+ Channels
|
|
Kim Sun-Oh
Rhim Hye-Whon
|
|
|
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+ chan-nels have been known to be closely involved in the mecha-nisms underlying the neurodegenerative properties of amyloid-beta (Abeta) peptides. However, most studies of L-type Ca2+ channels in Abeta-related mechanisms have been limited to CaV1.2, and surprisingly little is known about the involvement of CaV1.3 in Abeta-induced neuronal toxicity. In the present study, we examined the expression patterns of CaV1.3 after Abeta25-35 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 Abeta25-35 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 Abeta25-35, but not by Abeta35-25. We next found that acute treatment with A?25-35 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 beta3 subunits of Ca2+ channels instead of CaV1.2 or CaV1.3 alpha1 subunits. These results show that A?25-35 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.
|
|
|
KEYWORD
|
|
|
Alzheimer’s disease, co-immunoprecipitation, GST pulldown, intracellular Ca2+ L-type Ca2+ channels
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|