Neuronal distribution and functional characterization of the calcium channel alpha(2)delta-2 subunit

The auxiliary calcium channel alpha(2)delta subunit comprises a family of t hree 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 identifi cation and functional characterization of alpha(2)delta-2 splice variants a nd their mRNA distribution in the mouse brain. The splice variants differ i n the alpha(2) and delta protein by eight and three amino acid residues, re spectively, and are differentially expressed in cardiac tissue and human me dullary thyroid carcinoma (hMTC) cells. In situ hybridization of mouse brai n sections revealed the highest expression of alpha(2)delta-2 mRNA in the P urkinje cell layer of the cerebellum, habenulae and septal nuclei, and a lo wer expression in the cerebral cortex, olfactory bulb, thalamic and hypotha lamic nuclei, as well as the inferior and superior colliculus. As the in si tu data did not suggest a specific colocalization with any al subunit, coex pression studies of alpha(2)delta-2 were carried out either with the high-v oltagegated calcium channels, alpha(1c), alpha(1E) or alpha(1A), or with th e low-voltage-gated calcium channel, alpha(1G). Coexpression of alpha(2)del ta-2 increased the current density, shifted the voltage dependence of chann el activation and inactivation of alpha(1C), alpha(1E) and alpha(1A) subuni ts in a hyperpolarizing direction, and accelerated the decay and shifted th e steady-state inactivation of the alpha(1G) current.