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.