Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons

The importance and diversity of calcium signaling in the brain is mirrored by the expression of a multitude of voltage-activated calcium channel (CaV) isoforms. Whereas the overall distributions of α1 subunits are well established, the expression patterns of distinct channel isoforms in specific brain regions and neurons, as well as those of the auxiliary β and α2δ subunits are still incompletely characterized. Further it is unknown whether neuronal differentiation and activity induce changes of CaV subunit composition. Here we combined absolute and relative quantitative TaqMan reverse transcription PCR (RT-PCR) to analyze mRNA expression of all high voltage-activated CaV α1 subunits and all β and α2δ subunits. This allowed for the first time the direct comparison of complete CaV expression profiles of mouse cortex, hippocampus, cerebellum, and cultured hippocampal neurons. All brain regions expressed characteristic profiles of the full set of isoforms, except CaV1.1 and CaV1.4. In cortex development was accompanied by a general down regulation of α1 and α2δ subunits and a shift from β1/β3 to β2/β4. The most abundant CaV isoforms in cerebellum were CaV2.1, β4, and α2δ-2, and in hippocampus CaV2.3, β2, and α2δ-1. Interestingly, cultured hippocampal neurons also expressed the same CaV complement as adult hippocampus. During differentiation specific CaV isoforms experienced up- or down-regulation; however blocking electrical activity did not affect CaV expression patterns. Correlation analysis of α1, β and α2δ subunit expression throughout all examined preparations revealed a strong preference of CaV2.1 for β4 and α2δ-2 and vice versa, whereas the other α1 isoforms were non-selectively expressed together with each of the other β and α2δ isoforms. Together our results revealed a remarkably stable overall Ca2+ channel complement as well as tissue specific differences in expression levels. Developmental changes are likely determined by an intrinsic program and not regulated by changes in neuronal activity.