Calcium-dependent hyperexcitability of hippocampal CA1 pyramidal cells in an in vitro slice after ethanol withdrawal of the rat.
The physiological profiles contributing to hyperexcitability of hippocampal CA1 neurons following ethanol withdrawal (EW) were examined in an in vitro slice preparation obtained from EW rats. Sixty-two percent of CA1 neurons in slices from EW rats exhibited intrinsic burst property which was rarely observed in those from control animals. The mean duration of plateau component of calcium (Ca) spikes was significantly increased after EW. The burst response evoked by either synaptic or direct stimulation in hippocampal CA1 neurons from EW rats was markedly depressed by high Mg solution but not by flunarizine. Furthermore, 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA receptor antagonist, markedly depressed the synaptically evoked burst response, while [(+/-)-2-carboxypiperazine-4-yl-]-propyl-1-phosphonic acid, a selective N-methyl-D-aspartate (NMDA) receptor antagonist, slightly delayed the onset of the response. The results indicate that an increase in the number of bursting hippocampal CA1 neurons associated with an augmentation of the plateau component of Ca spike contributes to the genesis of hyperexcitability in EW rats. Furthermore, non-NMDA receptor-mediated EPSP is mainly responsible for a synaptic induction of the burst response. These results are consistent with the involvement of high-threshold Ca channels in EW hyperexcitability.
Shindou
T
T
Department of Pharmacology, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Watanabe
S
S
Kamata
O
O
Yamamoto
K
K
Nakanishi
H
H
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004594:Electrophysiology; D000431:Ethanol / Q000009:adverse effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D002118:Calcium