Neuronal distribution and functional characterization of the calcium channel α2δ-2 subunit

The auxiliary calcium channel alpha(2)delta subunit comprises a family of three genes, alpha(2)delta-1 to 3, which are expressed in a tissue-specific manner. alpha(2)delta-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 alpha(2)delta-2 splice variants and their mRNA distribution in the mouse brain. The splice variants differ in the alpha(2) and delta 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 alpha(2)delta-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 al subunit, coexpression studies of alpha(2)delta-2 were carried out either with the high-voltagegated calcium channels, alpha(1c), alpha(1E) or alpha(1A), or with the low-voltage-gated calcium channel, alpha(1G). Coexpression of alpha(2)delta-2 increased the current density, shifted the voltage dependence of channel activation and inactivation of alpha(1C), alpha(1E) and alpha(1A) subunits in a hyperpolarizing direction, and accelerated the decay and shifted the steady-state inactivation of the alpha(1G) current.