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Mol. Cells 2011; 32(3): 289-294

Published online September 30, 2011

https://doi.org/10.1007/s10059-011-0075-x

© The Korean Society for Molecular and Cellular Biology

Effects of Amyloid-β Peptides on Voltage-Gated L-Type CaV1.2 and CaV1.3 Ca2+ Channels

Sunoh Kim1, and Hyewhon Rhim2,*

1Jeollanamdo Institute of Natural Resources Research, Jangheung 529-851, Korea, 2Biomedical Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea

Correspondence to : *Correspondence: hrhim@kist.re.kr

Received: April 15, 2011; Revised: May 18, 2011; Accepted: June 24, 2011

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.

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

Article

Research Article

Mol. Cells 2011; 32(3): 289-294

Published online September 30, 2011 https://doi.org/10.1007/s10059-011-0075-x

Copyright © The Korean Society for Molecular and Cellular Biology.

Effects of Amyloid-β Peptides on Voltage-Gated L-Type CaV1.2 and CaV1.3 Ca2+ Channels

Sunoh Kim1, and Hyewhon Rhim2,*

1Jeollanamdo Institute of Natural Resources Research, Jangheung 529-851, Korea, 2Biomedical Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea

Correspondence to:*Correspondence: hrhim@kist.re.kr

Received: April 15, 2011; Revised: May 18, 2011; Accepted: June 24, 2011

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.

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

Mol. Cells
May 31, 2022 Vol.45 No.5, pp. 273~352
COVER PICTURE
Fe2+ ion depletion-induced expression of BΔGFP at the early stage of leaf development (Choi et al., pp. 294-305).

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