Ca_V2 channel subtype expression in rat sympathetic neurons is selectively regulated by α₂δ subunits.

Type two voltage gated calcium (Ca_V2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability. ¹ Mechanisms that regulate Ca_V2 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_V2.2 and Ca_V2.3. ² We noted previously that heterologous expression of Ca_V2.1 but not Ca_V2.2 results in increased calcium current in SCG neurons. ³ In the present study, we extended these observations to show that both Ca_V2.1 and Ca_V2.3 expression resulted in increased calcium currents while Ca_V2.2 expression did not. Further, Ca_V2.1 could displace native Ca_V2.2 channels, but Ca_V2.3 expression could not. Heterologous expression of the individual accessory subunits α₂δ-1, α₂δ-2, α₂δ-3, or β4 alone failed to increase current density, suggesting that the calcium current ceiling when Ca_V2.2 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_V2.2 by recombinant channels. Both α₂δ-1 and α₂δ-2 seemed to promote Ca_V2.2 displacement by recombinant channel expression, while α₂δ-3 appeared to protect Ca_V2.2 from displacement. Thus, we observe a selective prioritization of Ca_V channel functional expression in neurons by specific α₂δ subunits. These data highlight a new function for α₂δ subtypes that could shed light on subtype selectivity of Ca_V2 membrane expression.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}