Regional Expression and Cellular Localization of the α1and β Subunit of High Voltage-Activated Calcium Channels in Rat Brain

Abstract

The neuronal high voltage-activated calcium channels are a family of ion channels composed from up to five different α 1 and four different β subunits. The neuronal distribution and subunit composition of calcium channels were investigated using subunit-specific antibodies and riboprobes. The β subunit-specific antibodies identified the presence of β 1a in skeletal muscle; β 2 in heart; and β 2, β 3, and β 4 in brain. The β 3 protein was widely distributed in rat brain, with prominent labeling of olfactory bulb, cortex, hippocampus, and habenula. The β 4 protein was also widely expressed, most prominently in the cerebellum. β 2 protein was expressed at only low levels.In situ hybridization with β subunit-specific riboprobes confirmed the differential expression pattern of the individual subunits. Hybridization with riboprobes specific for the α 1A,α 1B,α 1C, and α 1D subunits showed a broad distribution of α 1A and α 1B transcripts, whereas the expression level of α 1C and α 1D mRNA was lower and more spatially restricted. The overall expression pattern and cellular localization suggested that β 4 may associate predominantly, but probably not exclusively, with the α 1A subunit, and β 3 with the α 1B subunit. In certain brain areas such as the habenula, the β 3 subunit may associate with other α 1 subunits too. Furthermore, the β 2 subunit may form complexes with different α 1 subunits in brain and cardiac muscle. These results demonstrate that a given β subunit may associate with different α 1 subunits in a cell type-dependent manner, contributing to the diversity of the neuronal calcium channels.