Voltage-dependent calcium channel abnormalities in hippocampal CA3 neurons of spontaneously epileptic rats.
OBJECTIVE
Hippocampal CA3 neurons of spontaneously epileptic rats (SER; zi/zi, tm/tm), which show both absence-like seizures and tonic convulsions, exhibit a long-lasting depolarization shift with repetitive firing with a single stimulation of mossy fibers. Therefore a whole-cell patch-clamp study using temporarily dissociated hippocampal CA3 neurons from SER was performed to elucidate whether such abnormal excitability was due to abnormalities in voltage-dependent Ca(2+) channels (VDCCs).


METHODS
Hippocampal CA3 neurons were temporarily dissociated with enzymatic and mechanical treatments. In a voltage-clamp mode with whole-cell recording, depolarizing step pulses were applied to induce Ca(2+) currents in the presence of tetrodotoxin and tetraethylammonium.


RESULTS
The threshold level of the Ca(2+) current induced by depolarizing pulses was found to be lower in hippocampal CA3 neurons of SER compared with those of control Wistar rats. In addition, the Ca(2+) current peak amplitude was greater, and decay of the current was weaker in CA3 neurons of SER than in those of normal Wistar rats.


CONCLUSIONS
These findings suggest that enhancements of Ca(2+) influx into hippocampal CA3 neurons due to the easier activation properties of VDCCs, as well as a decrease in decay, are involved in SER epileptic seizures.
Yan
Hai-Dun
HD
Department of Pharmacology, Hiroshima University School of Medicine, Hrioshima, Japan.
Ishihara
Kumatoshi
K
Hanaya
Ryosuke
R
Kurisu
Kaoru
K
Serikawa
Tadao
T
Sasa
Masashi
M
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D005452:Fluoresceins; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009930:Organic Chemicals; D018408:Patch-Clamp Techniques; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D019789:Tetraethylammonium; D013779:Tetrodotoxin
D015220:Calcium Channels; D005452:Fluoresceins; D009930:Organic Chemicals; C435731:fluoro jade; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D002118:Calcium