Molecular Diversity of the Calcium Channel α2δ Subunit

Abstract

Sequence database searches with the α 2 δ 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 α 2 δ-2 and α 2 δ-3 subunits share 55.6 and 30.3% identity with the α 2 δ-1 subunit, respectively. The number of putative glycosylation sites and cysteine residues, hydropathicity profiles, and electrophysiological character of the α 2 δ-3 subunit indicates that these proteins are functional calcium channel subunits. Coexpression of α 2 δ-3 with α 1C and cardiac β2a or α 1E and 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 α 2 δ-1 or α 2 δ-3 was expressed with α 1C. The effects of α 2 δ-3 on α 1C but not α 1E are indistinguishable from the effects of α 2 δ-1. Using Northern blot analysis, it was shown that α 2 δ-3 is expressed exclusively in brain, whereas α 2 δ-2 is found in several tissues.In situ hybridization of mouse brain sections showed mRNA expression of α 2 δ-1 and α 2 δ-3 in the hippocampus, cerebellum, and cortex, with α 2 δ-1 strongly detected in the olfactory bulb and α 2 δ-3 in the caudate putamen.