Increased expression of P/Q-type Ca2+ channel alpha1A subunit mRNA in cerebellum of N-type Ca2+ channel alpha1B subunit gene-deficient mice.

The Ca(2+) channel alpha(1B) subunit is a pore-forming component capable of generating N-type Ca(2+) channel activity. Although the N-type Ca(2+) channel plays a role in a variety of neuronal functions, alpha(1B)-deficient mice show normal behavior, presumably owing to compensation by the other Ca(2+) channels. In this study, we examined the mRNA expression of the P/Q-type Ca(2+) channel alpha(1A) subunit in cerebellum of alpha(1B)-deficient mice. The alpha(1A) subunit mRNA in homozygous alpha(1B)-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 alpha(1A) subunit gene, we examined lacZ expression in alpha(1B)-deficient x alpha(1A)3.0-lacZ mice (carrying a 3.0-kb 5'-upstream fragment of the alpha(1A) subunit gene fused to Escherichia coli lacZ reporter gene), which express lacZ in granule but not in Purkinje cells, and in alpha(1B)-deficient x alpha(1A)6.3-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 alpha(1B)-deficient x alpha(1A)3.0-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 alpha(1B)-deficient x alpha(1A)6.3-lacZ mice. Therefore, a possible explanation of the normal behavior of alpha(1B)-deficient mice is that compensation by alpha(1A) subunit gene occurs and that the 3.0-kb 5'-upstream region of alpha(1A) subunit gene contains an enhancer cis-element(s) for compensation in cerebellar granule cells.