Enhanced Calcium Influx in Hippocampal CA3 Neurons of Spontaneously Epileptic Rats

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 Ca2+ channel abnormalities. The present study was performed to determine whether Ca2+ 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 Ca2+ concentration ([Ca2+]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 [Ca2+]i in hippocampal CA1, CA3, and dentate gyrus (DG) areas of both the normal rats and SER in a concentration‐dependent manner. However, the high K+–induced increase in [Ca2+]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 [Ca2+]i in CA1 or DG between the SER and controls. The high K+–induced increases in [Ca2+]i of CA1, CA3, and DG were inhibited by nifedipine (1∼10 nM), a Ca2+ channel antagonist in both SER and controls. However, the inhibition of the high K+–induced increase in [Ca2+]i by nifedipine (1 nM) was significantly greater in the CA3 area of SER than that of controls.Conclusions: These findings suggest that Ca2+ influx through the L‐type Ca2+ 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.