Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats

Noda epileptic rat (NER) is a mutant rat, which spontaneously exhibits a tonic-clonic convulsion from 14 weeks of age. An intracellular recording study was performed to elucidate the abnormal excitability of NER hippocampal CA3 neurons. The recorded neurons were classified into two groups, group A a...

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Main Authors: Yoshihiro Kiura, Ryosuke Hanaya, Tadao Serikawa, Kaoru Kurisu, Norio Sakai, Masashi Sasa
Format: Article
Language:English
Published: Elsevier 2003-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319327537
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author Yoshihiro Kiura
Ryosuke Hanaya
Tadao Serikawa
Kaoru Kurisu
Norio Sakai
Masashi Sasa
author_facet Yoshihiro Kiura
Ryosuke Hanaya
Tadao Serikawa
Kaoru Kurisu
Norio Sakai
Masashi Sasa
author_sort Yoshihiro Kiura
collection DOAJ
description Noda epileptic rat (NER) is a mutant rat, which spontaneously exhibits a tonic-clonic convulsion from 14 weeks of age. An intracellular recording study was performed to elucidate the abnormal excitability of NER hippocampal CA3 neurons. The recorded neurons were classified into two groups, group A and B neurons, according to the responses to a single stimulation of mossy fibers. In group A neurons, a stimulus elicited a long-lasting depolarization shift accompanying repetitive firings followed by after-hyperpolarization. In group B neurons, the same stimulus elicited a single spike without a long-lasting depolarization shift. Bath application of 1 mM Cd2+, a nonselective Ca2+ channel blocker, completely inhibited the abnormal excitation in group A neurons. We further examined the character of Ca2+ spikes in NER CA3 neurons. Ca2+ spikes were completely blocked by 10 μM Cd2+ in group A neurons, but not in either group B or control neurons, suggesting that Ca2+ channels in NER group A neurons have the hypersensitivity to Cd2+. Analysis using subtype specific blockers of Ca2+ channel raised the possible involvement of T-type Ca2+ channels. These results suggest that Ca2+ channel dysfunction is involved in the abnormal excitability of CA3 pyramidal neurons and pathogenesis of epilepsy in NER.
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spelling doaj.art-0f927983c2c44489aeafd7932d5ae9182022-12-21T19:30:18ZengElsevierJournal of Pharmacological Sciences1347-86132003-01-01912137144Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic RatsYoshihiro Kiura0Ryosuke Hanaya1Tadao Serikawa2Kaoru Kurisu3Norio Sakai4Masashi Sasa5Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan; Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanInstitute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, JapanDepartment of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanNagisa Hospital, Osaka 573-1183, JapanNoda epileptic rat (NER) is a mutant rat, which spontaneously exhibits a tonic-clonic convulsion from 14 weeks of age. An intracellular recording study was performed to elucidate the abnormal excitability of NER hippocampal CA3 neurons. The recorded neurons were classified into two groups, group A and B neurons, according to the responses to a single stimulation of mossy fibers. In group A neurons, a stimulus elicited a long-lasting depolarization shift accompanying repetitive firings followed by after-hyperpolarization. In group B neurons, the same stimulus elicited a single spike without a long-lasting depolarization shift. Bath application of 1 mM Cd2+, a nonselective Ca2+ channel blocker, completely inhibited the abnormal excitation in group A neurons. We further examined the character of Ca2+ spikes in NER CA3 neurons. Ca2+ spikes were completely blocked by 10 μM Cd2+ in group A neurons, but not in either group B or control neurons, suggesting that Ca2+ channels in NER group A neurons have the hypersensitivity to Cd2+. Analysis using subtype specific blockers of Ca2+ channel raised the possible involvement of T-type Ca2+ channels. These results suggest that Ca2+ channel dysfunction is involved in the abnormal excitability of CA3 pyramidal neurons and pathogenesis of epilepsy in NER.http://www.sciencedirect.com/science/article/pii/S1347861319327537
spellingShingle Yoshihiro Kiura
Ryosuke Hanaya
Tadao Serikawa
Kaoru Kurisu
Norio Sakai
Masashi Sasa
Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats
Journal of Pharmacological Sciences
title Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats
title_full Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats
title_fullStr Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats
title_full_unstemmed Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats
title_short Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats
title_sort involvement of ca2 channels in abnormal excitability of hippocampal ca3 pyramidal cells in noda epileptic rats
url http://www.sciencedirect.com/science/article/pii/S1347861319327537
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