The expression of voltage-dependent calcium channel beta subunits in human hippocampus

Abstract

The β subunits of voltage-dependent calcium channels (VDCC) modulate the electrophysiology and cell surface expression of pore-forming α 1 subunits. In the present study we have investigated the distribution of β 1,β 2,β 3 and β 4 in the human hippocampus using in situ hybridization (ISH) and immunohistochemistry. ISH studies showed a similar distribution of expression of β 1,β 2 and β 3 subunit mRNAs, including labelling of the dentate granule cell layer, all CA pyramidal regions, and the subiculum. Relatively low levels of expression of β 1 and β 2 subunit mRNAs correlated with low protein expression in the immunocytochemical (ICC) studies. There was a relative lack of β 4 expression by both ISH and ICC in the CA1 region, compared with high levels of expression in the subiculum. Immunostaining for β 1 and β 2 subunits was weak and relatively homogeneous throughout the hippocampus. The β 3 and β 4 subunits appeared to be more discretely localized. In general, β 3-immunoreactivity was moderate both in cell bodies, and as diffuse staining in the surrounding neuropil. Strongest staining was observed in mossy fibres and their terminal region in the CA3 stratum lucidum. In contrast, β 4-immunoreactivity in the neuropil showed intense dendritic localisation. Unlike the other subunits, β 4-immunoreactivity was absent from CA1 pyramidal neurones but was present in a small population of interneurone-like cells. The localisation of β 3 and β 4 may represent presynaptic and postsynaptic compartments in some populations of hippocampal neurones. Comparison of β subunit distribution with previously published data on α 1 subunits indicates certain neuronal groups and subcellular compartments in which the subunit composition of native pre- and postsynaptic VDCC can be predicted.