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This Article Full Text Full Text (PDF) All Versions of this Article: 93/4/1845    most recent 00656.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Skov, J. Articles by Andreasen, M. Search for Related Content PubMed PubMed Citation Articles by Skov, J. Articles by Andreasen, M.

New Type of Synaptically Mediated Epileptiform Activity Independent of Known Glutamate and GABA Receptors

Institute of Physiology and Biophysics, Department of Physiology, University of Aarhus, Denmark

Submitted 9 June 2004; accepted in final form 3 November 2004

It is well known that excitatory synaptic transmission at the hippocampal CA3–CA1 synapse depends on the binding of released glutamate to ionotropic receptors. Here we report that during long-term application of Cs⁺ (5 mM), stimulation of the Schaffer collateral-commisural pathway evokes an epileptic field potential (Cs-FP) in area CA1 of the rat hippocampal slice, which is resistant to antagonists of ionotropic glutamate and GABA_A receptors. The Cs-FP was blocked by N-type but not L-type Ca²⁺ channel antagonists and was attenuated by adenosine (0.5 mM), as expected for a synaptically mediated response. These properties make the Cs-FP fundamentally different from other types of Cs⁺-induced epileptiform activity. Replacement of Cs⁺ with antagonists of the hyperpolarization-activated nonselective cation current I_h and inwardly rectifying potassium channels (K_IR) or partial inhibition of the Na⁺/K⁺ pump did not cause Cs-FP–like potentials, which indicates that such actions of Cs⁺ were not responsible for the Cs-FP. The effect of Cs⁺ was partly mimicked by 4-aminopyridine (4-AP; 2 mM), suggesting that an increase in transmitter release is involved. The group I metabotropic glutamate receptor (mGluR) agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) attenuated the Cs-FP. This effect was not, however, antagonized by group I mGluR antagonists. Selective and nonselective mGluR antagonists did not attenuate the Cs-FP. We conclude that long-term exposure to Cs⁺ induces a state where excitatory synaptic transmission can exist between area CA3 and CA1 in the hippocampus, independent of ionotropic and metabotropic glutamate receptors and GABA_A receptors.