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, pharmacological and electrophysiological data indicate a significant but undisclosed role for voltage-dependent calcium channels. Since the contribution such channels make to nerve function reflects the targeting of discrete subtypes to distinct cellular regions, we hypothesized that epilepsy reflects alterations 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. Confocal microscopy of N-type calcium channels labeled with a new fluorescent ligand, coupled with a novel technique for analysing multiple images, revealed 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 with cell number or synaptogenesis, but are consistent with increased N-type calcium channel expression on presynaptic terminals or, more likely, dendrites. These data rationalize recent electrophysiology and in situ hybridization data, and suggest that kindling alters N-type calcium channel trafficking mechanisms to cause a persistent, local, remodeling of their distributions in CA1 dendrites. The persistent induction of N-type calcium channels may be part of a mechanism for, and a hallmark of, synaptic plasticity, in which kindling represents a reinforcement of synapses en masse.
Bernstein
G M
GM
Playfair Neuroscience Unit, MC11-434, Toronto Hospital Research Institute, Toronto Hospital Western Division, Ontario, Canada.
Mendonça
A
A
Wadia
J
J
Burnham
W M
WM
Jones
O T
OT
D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002232:Carbocyanines; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D018613:Microscopy, Confocal; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors; D020960:omega-Conotoxins
D020864:Calcium Channels, N-Type; D002232:Carbocyanines; D005456:Fluorescent Dyes; C089187:cyanine dye 3; D020960:omega-Conotoxins