Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats

Abstract

Noda epileptic rat (NER) is a mutant rat, which spontaneously exhibits a tonic-clonic convulsion from 14 weeks of age. An intracellular recording study was performed to elucidate the abnormal excitability of NER hippocampal CA3 neurons. The recorded neurons were classified into two groups, group A and B neurons, according to the responses to a single stimulation of mossy fibers. In group A neurons, a stimulus elicited a long-lasting depolarization shift accompanying repetitive firings followed by after-hyperpolarization. In group B neurons, the same stimulus elicited a single spike without a long-lasting depolarization shift. Bath application of 1 mM Cd2+, a nonselective Ca2+ channel blocker, completely inhibited the abnormal excitation in group A neurons. We further examined the character of Ca2+ spikes in NER CA3 neurons. Ca2+ spikes were completely blocked by 10 μM Cd2+ in group A neurons, but not in either group B or control neurons, suggesting that Ca2+ channels in NER group A neurons have the hypersensitivity to Cd2+. Analysis using subtype specific blockers of Ca2+ channel raised the possible involvement of T-type Ca2+ channels. These results suggest that Ca2+ channel dysfunction is involved in the abnormal excitability of CA3 pyramidal neurons and pathogenesis of epilepsy in NER.