N. Klugbauer

The auxiliary calcium channel α₂δ subunit comprises a family of three genes, α₂δ‐1 to 3, which are expressed in a tissue‐specific manner. α₂δ‐2 mRNA is found in the heart, skeletal muscle, brain, kidney, liver and pancreas. We report here for the first time the identification and functional characterization of α₂δ‐2 splice variants and their mRNA distribution in the mouse brain. The splice variants differ in the α₂ and δ protein by eight and three amino acid residues, respectively, and are differentially expressed in cardiac tissue and human medullary thyroid carcinoma (hMTC) cells. In situ hybridization of mouse brain sections revealed the highest expression of α₂δ‐2 mRNA in the Purkinje cell layer of the cerebellum, habenulae and septal nuclei, and a lower expression in the cerebral cortex, olfactory bulb, thalamic and hypothalamic nuclei, as well as the inferior and superior colliculus. As the in situ data did not suggest a specific colocalization with any α₁ subunit, coexpression studies of α₂δ‐2 were carried out either with the high‐voltage‐gated calcium channels, α_1C, α_1E or α_1A, or with the low‐voltage‐gated calcium channel, α_1G. Coexpression of α₂δ‐2 increased the current density, shifted the voltage dependence of channel activation and inactivation of α_1C, α_1E and α_1A subunits in a hyperpolarizing direction, and accelerated the decay and shifted the steady‐state inactivation of the α_1G current.