The Ca2+ channel α1B subunit is a pore-forming component capable of generating N-type Ca2+ channel activity. Although the N-type Ca2+ channel plays a role in a variety of neuronal functions, α1B-deficient mice show normal behavior, presumably owing to compensation by the other Ca2+ channels. In this study, we examined the mRNA expression of the P/Q-type Ca2+ channel α1A subunit in cerebellum of α1B-deficient mice. The α1A subunit mRNA in homozygous α1B- deficient mice was expressed at a significantly higher level than in wild or heterozygous mice. To examine whether the increased expression is induced by a cis-regulatory element within the 5′-upstream region of the α1A subunit gene, we examined lacZ expression in α1B-deficient×α1A3.0-lacZ mice (carrying a 3.0-kb 5′-upstream fragment of the α1A subunit gene fused to Escherichia coli lacZ reporter gene), which express lacZ in granule but not in Purkinje cells, and in α1B- deficient×α1A6.3-lacZ mice (carrying a 6.3-kb 5′-upstream region fused to lacZ gene), which express lacZ in Purkinje but not in granule cells. The levels of lacZ expression in homozygous α1B-deficient×α1A3.0-lacZ mice were significantly higher than in wild or heterozygous mice, but no difference in lacZ expression level was found among wild, heterozygous and homozygous α1B-deficient×α1A6.3-lacZ mice. Therefore, a possible explanation of the normal behavior of α 1B-deficient mice is that compensation by α1A subunit gene occurs and that the 3.0-kb 5′-upstream region of α1A subunit gene contains an enhancer cis-element(s) for compensation in cerebellar granule cells.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cellular and Molecular Neuroscience