Molecular Diversity of the Calcium Channel α2δ Subunit

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Abstract
Sequence database searches with the α2δ subunit as probe led to the identification of two new genes encoding proteins with the essential properties of this calcium channel subunit. Primary structure comparisons revealed that the novel α2δ-2 and α2δ-3 subunits share 55.6 and 30.3% identity with the α2δ-1 subunit, respectively. The number of putative glycosylation sites and cysteine residues, hydropathicity profiles, and electrophysiological character of the α2δ-3 subunit indicates that these proteins are functional calcium channel subunits. Coexpression of α2δ-3 with α1Cand cardiac β2a or α1Eand β3 subunits shifted the voltage dependence of channel activation and inactivation in a hyperpolarizing direction and accelerated the kinetics of current inactivation. The kinetics of current activation were altered only when α2δ-1 or α2δ-3 was expressed with α1C. The effects of α2δ-3 on α1Cbut not α1Eare indistinguishable from the effects of α2δ-1. Using Northern blot analysis, it was shown that α2δ-3 is expressed exclusively in brain, whereas α2δ-2 is found in several tissues.In situhybridization of mouse brain sections showed mRNA expression of α2δ-1 and α2δ-3 in the hippocampus, cerebellum, and cortex, with α2δ-1 strongly detected in the olfactory bulb and α2δ-3 in the caudate putamen.