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Ca V 2 channel subtype expression in rat sympathetic neurons is selectively regulated by α 2 δ subunits

Type two voltage gated calcium (Ca 2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability. Mechanisms that regulate Ca 2 channel expression at synapses have been studied extensively, which mot...

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Bibliographic Details
Published in:Channels (Austin, Tex.) Tex.), 2017-11, Vol.11 (6), p.555-573
Main Authors: Scott, Mallory B, Kammermeier, Paul J
Format: Article
Language:English
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Summary:Type two voltage gated calcium (Ca 2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability. Mechanisms that regulate Ca 2 channel expression at synapses have been studied extensively, which motivated us to perform similar studies in the soma. Rat sympathetic neurons from the superior cervical ganglion (SCG) natively express Ca 2.2 and Ca 2.3. We noted previously that heterologous expression of Ca 2.1 but not Ca 2.2 results in increased calcium current in SCG neurons. In the present study, we extended these observations to show that both Ca 2.1 and Ca 2.3 expression resulted in increased calcium currents while Ca 2.2 expression did not. Further, Ca 2.1 could displace native Ca 2.2 channels, but Ca 2.3 expression could not. Heterologous expression of the individual accessory subunits α δ-1, α δ-2, α δ-3, or β4 alone failed to increase current density, suggesting that the calcium current ceiling when Ca 2.2 was over-expressed was not due to lack of these subunits. Interestingly, introduction of recombinant α2δ subunits produced surprising effects on displacement of native Ca 2.2 by recombinant channels. Both α δ-1 and α δ-2 seemed to promote Ca 2.2 displacement by recombinant channel expression, while α δ-3 appeared to protect Ca 2.2 from displacement. Thus, we observe a selective prioritization of Ca channel functional expression in neurons by specific α δ subunits. These data highlight a new function for α δ subtypes that could shed light on subtype selectivity of Ca 2 membrane expression.
ISSN:1933-6950
1933-6969
DOI:10.1080/19336950.2017.1356954