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Volume 17, Number 4, Issue of February 15, 1997 pp. 1339-1349
Copyright ©1997 Society for Neuroscience

Regional Expression and Cellular Localization of the alpha 1 and beta  Subunit of High Voltage-Activated Calcium Channels in Rat Brain

Received Sept. 13, 1996; revised Dec. 2, 1996; accepted Dec. 13, 1996.

Andreas Ludwig, Veit Flockerzi, and Franz Hofmann

Institut für Pharmakologie und Toxikologie der Technischen Universität München, 80802 München, Germany

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

Key words: ion channel; calcium channel; brain; hippocampus; cerebellum; olfactory bulb; habenula




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