Differential alterations in the distribution of voltage-gated calcium channels in aged rat cerebellum

In the present study, we used immunohistochemistry and Western blot analysis to determine region-specific changes in the distribution of voltage-gated calcium channels (VGCCs) in aged rat cerebellum. Age-dependent changes in the staining intensity of the alpha(1C) and alpha(1D) subunits were prominent in the Purkinje cells, whereas there was no change in the expression of the alpha(1A) and alpha(1B) subunits. In the aged rat, in particular, immunoreactivity for the alpha(1C) subunits were increased in the dendrites as well as in the cell bodies of Purkinje cells. On the other hand, decreases in immunoreactivity for alpha(1A) and alpha(1D) subunits were found in the molecular or granular layers. However, only alpha(1D) subunit immunoreactivity was decreased in the aged cerebellum membrane by Western blot analysis that, while not addressing regional specificity, further confirmed an age-related decrease in alpha(1D) subunit. These age-related changes in alpha(1D) subunit expression might reflect a gradual loss of regulation for L-type Ca(2+) channels in the senescent period. The first demonstration of age-related alterations in VGCC expression may provide useful data for future investigations on aging and neurodegenerative diseases.