Kindling induces a long-term enhancement in the density of N-type calcium channels in the rat hippocampus

How seizures arise and recur in epilepsy is unknown. Recent genetic, pharma cological and electrophysiological data indicate a significant but undisclo sed role for voltage-dependent calcium channels. Since the contribution suc h channels make to nerve function reflects the targeting of discrete subtyp es to distinct cellular regions, we hypothesized that epilepsy reflects alt erations in their spatiotemporal patterns of expression at the cell surface . To test this possibility, we examined the expression and distribution of hippocampal N-type calcium channels in an animal seizure model: kindling. C onfocal microscopy of N-type calcium channels labeled with a new fluorescen t ligand, coupled with a novel technique for analysing multiple images, rev ealed a 20-40% increase in their expression in CA1 and CA3 within 24 h post -seizure. These increases persisted in the dendritic fields of CA1, but had dissipated in CA3 by 28 days post-seizure. Such changes correlate poorly w ith cell number or synaptogenesis, but are consistent with increased N-type calcium channel expression on presynaptic terminals or, more likely, dendr ites. These data rationalize recent electrophysiology and in situ hybridization d ata, and suggest that kindling alters N-type calcium channel trafficking me chanisms to cause a persistent, local, remodeling of their distributions in CAI dendrites. The persistent induction of N-type calcium channels may be part of a mechanism for, and a hallmark of, synaptic plasticity, in which k indling represents a reinforcement of synapses en masse. (C) 1999 IBRO. Pub lished by Elsevier Science Ltd.