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Enhanced Calcium Influx in Hippocampal CA3 Neurons of Spontaneously Epileptic Rats
Author(s) -
Amano Hiroko,
Amano Taku,
Matsubayashi Hiroaki,
Ishihara Kumatoshi,
Serikawa Tadao,
Sasa Masashi
Publication year - 2001
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2001.11300.x
Subject(s) - hippocampal formation , dentate gyrus , chemistry , nifedipine , depolarization , epilepsy , endocrinology , stimulation , medicine , hippocampus , calcium , neuroscience , biology
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 m M ) 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 concentration‐dependent 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 n M ), 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 n M ) 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.