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Expression and Subunit Interaction of Voltage-Dependent Ca2+ Channels in PC12 Cells
Journal article   Open access   Peer reviewed

Expression and Subunit Interaction of Voltage-Dependent Ca2+ Channels in PC12 Cells

Hongyan Liu, Ricardo Felix, Christina A Gurnett, Michel De Waard, Derrick R Witcher and Kevin P Campbell
The Journal of neuroscience, Vol.16(23), pp.7557-7565
12/01/1996
DOI: 10.1523/JNEUROSCI.16-23-07557.1996
PMID: 8922412
url
https://doi.org/10.1523/JNEUROSCI.16-23-07557.1996View
Published (Version of record) Open Access

Abstract

Nerve growth factor (NGF)-induced differentiation in PC12 cells is accompanied by changes in the expression of voltage-dependent Ca 2+ channels. Ca 2+ channels are multimeric complexes composed of at least three subunits (α 1 , β, and α 2 δ) and are involved in neuronal migration, gene expression, and neurotransmitter release. Although attempts have been undertaken to elucidate NGF regulation of Ca 2+ channel expression, the changes in subunit composition of these channels during differentiation still remain uncertain. In the present study, patch-clamp recordings show that in addition to the previously documented L-type and N-type Ca 2+ currents, undifferentiated PC12 cells also express an ω-agatoxin-IVA-sensitive (P/Q-type) component. In addition, the corresponding mRNA encoding the pore-forming α 1 subunits for these channels (C, B, and A, respectively) was detected. Likewise, mRNA for three distinct auxiliary β subunits (1, 2, 3) were also found, β 3 protein being dominantly expressed. Immunoprecipitation experiments show that the N-type Ca 2+ channel is associated with either a β 2 or β 3 subunit and that NGF increases the channel expression without affecting its β subunit association. These results (1) indicate that the diversity of Ca 2+ currents in PC12 cells arise from the expression of three distinct α 1 and three different β subunit genes; (2) support a model for heterogenous β subunit association of the N-type Ca 2+ channel in a single cell type; and (3) suggest that the regulation of the N-type Ca 2+ channel during NGF-mediated differentiation involves an increase in the number of functional channels with no apparent changes in subunit composition.
P β subunit PC12 ω-agatoxin-IVA N-type nerve growth factor calcium channels α1B subunit ω-conotoxin GVIA Q-type

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