Ca2 channel subtype expression in rat sympathetic neurons is selectively regulated by αδ subunits.

Type two voltage gated calcium (Ca2) 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 Ca2 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 Ca2.2 and Ca2.3. We noted previously that heterologous expression of Ca2.1 but not Ca2.2 results in increased calcium current in SCG neurons. In the present study, we extended these observations to show that both Ca2.1 and Ca2.3 expression resulted in increased calcium currents while Ca2.2 expression did not. Further, Ca2.1 could displace native Ca2.2 channels, but Ca2.3 expression could not. Heterologous expression of the individual accessory subunits αδ-1, αδ-2, αδ-3, or β4 alone failed to increase current density, suggesting that the calcium current ceiling when Ca2.2 was over-expressed was not due to lack of these subunits. Interestingly, introduction of recombinant α2δ subunits produced surprising effects on displacement of native Ca2.2 by recombinant channels. Both αδ-1 and αδ-2 seemed to promote Ca2.2 displacement by recombinant channel expression, while αδ-3 appeared to protect Ca2.2 from displacement. Thus, we observe a selective prioritization of Ca channel functional expression in neurons by specific αδ subunits. These data highlight a new function for αδ subtypes that could shed light on subtype selectivity of Ca2 membrane expression.