Abstract
Voltage-dependent Ca 2+ channels constitute a major class of plasma membrane channels through which a significant amount of extracellular Ca 2+ enters neuronal cells. Their pore-forming α 1 subunits are associated with cytoplasmic regulatory β subunits, which modify the distinct biophysical and pharmacological properties of the α 1 subunits. Studies in animal models indicate altered expression of α 1 and/or β subunits in epilepsy. We have focused on the regulatory β subunits and have analysed the immunoreactivity patterns of the β 1 , β 2 , β 3 and β 4 subunits in the hippocampus of patients with temporal lobe epilepsy ( n=18) compared to control specimens ( n=2). Temporal lobe epilepsy specimens were classified as Ammon's horn sclerosis ( n=9) or focal lesions without alteration of hippocampal cytoarchitecture ( n=9). Immunoreactivity for the β subunits was observed in neuronal cell bodies, dendrites and neuropil. The β 1, β 2 and β 3 subunits were found mainly in cell bodies while the β 4 subunit was primarily localized to dendrites. Compared to the control specimens, epilepsy specimens of the Ammon's horn sclerosis and of the lesion group showed a similar β subunit distribution, except for β 1 and β 2 staining in the Ammon's horn sclerosis group: in the severely sclerotic hippocampal subfields of these specimens, β 1 and β 2 immunoreactivity was enhanced in some of the remaining neuronal cell bodies and, in addition, strongly marked dendrites. Thus, hippocampal neurons apparently express multiple classes of β subunits which segregate into particular subcellular domains. In addition, the enhancement of β 1 and β 2 immunoreactivity in neuronal cell bodies and the additional shift of the β 1 and β 2 subunits into the dendritic compartment in severely sclerotic hippocampal regions indicate specific changes in Ammon's horn sclerosis. Altered expression of these β subunits may lead to increased currents carried by voltage-dependent calcium channels and to enhanced synaptic excitability.
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