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A role for Src kinase in spontaneous epileptiform activity in the CA3 region of the hippocampus

Academic Article
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Overview

authors

  • Sanna, Pietro
  • Berton, F.
  • Cammalleri, M.
  • Tallent, M. K.
  • Siggins, George
  • Bloom, Floyd
  • Francesconi, Valter

publication date

  • July 2000

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Members of the Src family of nonreceptor protein tyrosine kinases (PTKs) have been implicated in the regulation of cellular excitability and synaptic plasticity. We have investigated the role of these PTKs in in vitro models of epileptiform activity. Spontaneous epileptiform discharges were induced in vitro in the CA3 region of rat hippocampal slices by superfusion with the potassium channel blocker 4-aminopyridine in Mg(2+)-free medium. In hippocampal slices treated in this fashion, Src kinase activity was increased and the frequency of epileptiform discharges could be greatly reduced by inhibitor of the Src family of PTKs, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), but not by the inactive structural analog 4-amino-7-phenylpyrazol[3,4-d]pyrimidine (PP3). 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine also reduced epileptiform activity induced by either 4-aminopyridine or Mg(2+)-free medium alone. These observations demonstrate a role for Src family PTKs in the pathophysiology of epilepsy and suggest potential therapeutic targets for antiepileptic therapy.

subject areas

  • 2-Amino-5-phosphonovalerate
  • 4-Aminopyridine
  • Animals
  • Electrophysiology
  • Enzyme Inhibitors
  • Epilepsy
  • Excitatory Amino Acid Antagonists
  • Hippocampus
  • In Vitro Techniques
  • Magnesium
  • Male
  • Potassium Channel Blockers
  • Pyrimidines
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate
  • src-Family Kinases
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Identity

PubMed Central ID

  • PMC27003

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.140219097

PubMed ID

  • 10890901
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Additional Document Info

start page

  • 8653

end page

  • 8657

volume

  • 97

issue

  • 15

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