title: Enhanced calcium influx in hippocampal CA3 neurons of spontaneously epileptic rats.
abstract: OBJECTIVE
  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 abnorrmalities. 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 to approximately 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.
authors.affiliation: Department of Pharmacology, Hiroshima University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Amano
authors.forename: T
authors.initials: T
authors.lastname: Amano
authors.forename: H
authors.initials: H
authors.lastname: Matsubayashi
authors.forename: K
authors.initials: K
authors.lastname: Ishihara
authors.forename: T
authors.initials: T
authors.lastname: Serikawa
authors.forename: M
authors.initials: M
authors.lastname: Sasa
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000378:metabolism*; D016257:Fura-2 / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D009543:Nifedipine / Q000494:pharmacology; D010783:Photometry; D011189:Potassium Chloride / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D015220:Calcium Channels; D011189:Potassium Chloride; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2