Summary:Purpose: The spontaneously epileptic rat (SER: tm/tm, zi/zi) shows both absence-like seizures and tonic convulsions. Our previous electrophysiologic studies have demonstrated that SER has abnormal excitability of hippocampal CA3 neurons, which shows a long-lasting depolarization shift by a single stimulation of mossy fibers, probably resulting from the Ca 2+ channel abnormalities. The present study was performed to determine whether Ca 2+ influx is actually enhanced in the CA3 area of SER.Methods: Hippocampal slices were prepared from normal Wistar rats and SER aged 11-16 weeks old, when the epileptic seizures had been observed, and loaded with fura-2AM. Intracellular Ca 2+ concentration ([Ca 2+ ] i ) was monitored as the ratio of fluorescence intensities excited at wavelengths of 340 and 380 nm (RF340/F380) with photometric devices.Results: High K + (10∼60 mM) applied to the bath for 2 min increased [Ca 2+ ] i in hippocampal CA1, CA3, and dentate gyrus (DG) areas of both the normal rats and SER in a concentrationdependent manner. However, the high K + -induced increase in [Ca 2+ ] i was significantly more pronounced in the CA3 area of the SER than in that of the normal animals, whereas there were no significant differences in high K + -induced increases of [Ca 2+ ] i in CA1 or DG between the SER and controls. The high K + -induced increases in [Ca 2+ ] i of CA1, CA3, and DG were inhibited by nifedipine (1∼10 nM), a Ca 2+ channel antagonist in both SER and controls. However, the inhibition of the high K + -induced increase in [Ca 2+ ] i by nifedipine (1 nM) was significantly greater in the CA3 area of SER than that of controls.Conclusions: These findings suggest that Ca 2+ influx through the L-type Ca 2+ channels is much greater in the CA3 area of SER than in that of normal animals and is involved in the epileptic seizures of the SER. Key Words: Calcium influx-Spontaneously epileptic rat (SER)-Fura-2-Hippocampal CA3 area-KCl.Spontaneously epileptic rat (SER: tm/tm, zi/zi) is a double mutant obtained by mating tremor heterozygotes (tm/+), a mutant found in the Kyoto-Wistar closed colony (1,2), with zitter rat homozygotes (zi/zi), derived from a colony of Sprague-Dawley rats (3). After age 8-9 weeks, SERs spontaneously show a tonic convulsion and absence-like seizure characterized by the sudden appearance of 5-to 7-Hz spike-wave-like complexes in the cortical and hippocampal EEG concomitant with immobility and staring (4). Our previous studies suggested that the SER was a useful animal model for evaluation of short-and long-term effects of antiepileptic drugs (AEDs) (4,5), because the profile of the clinically available AEDs on the seizures of this animal resembled that in human epilepsy. In addition, our in vitro electrophysiologic study using brain slice preparations demonstrated that a long-lasting depolarization shift accompanied by repetitive firing was induced by a single stimulation of mossy fibers in the hippocampal CA3 region (6). Neuronal hyperexcitability has also been reported in hippocampal ...