Synaptic regulation of the slow Ca2+-activated K+ current in hippocampal CA1 pyramidal neurons: Implication in epileptogenesis

Eduardo D. Martín, Alfonso Araque, Washington Bunõ

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62 Scopus citations


The slow Ca2+-activated K+ current (sIAHP) plays a critical role in regulating neuronal excitability, but its modulation during abnormal bursting activity, as in epilepsy, is unknown. Because synaptic transmission is enhanced during epilepsy, we investigated the synaptically mediated regulation of the sIAHP and its control of neuronal excitability during epileptiform activity induced by 4-aminopyridine (4AP) or 4AP+Mg2+-free treatment in rat hippocampal slices. We used electrophysiological and photometric Ca2+ techniques to analyze the sIAHP modifications that parallel epileptiform activity. Epileptiform activity was characterized by slow, repetitive, spontaneous depolarizations and action potential bursts and was associated with increased frequency and amplitude of spontaneous excitatory postsynaptic currents and a reduced sIAHP. The metabotropic glutamate receptor (mGluR) antagonist (S)-α-methyl-4-carboxyphenylglycine did not modify synaptic activity enhancement but did prevent sIAHP inhibition and epileptiform discharges. The mGluRdependent regulation of the sIAHP was not caused by modulated intracellular Ca2+ signaling. Histamine, isoproterenol, and(±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid reduced the sIAPH but did not increase synaptic activity and failed to evoke epileptiform activity. We conclude that 4AP or 4AP+Mg-free-induced enhancement of synaptic activity reduced the sIAHP via activation of postsynaptic group I/II mGluRs. The increased excitability caused by the lack of negative feedback provided by the sIAHP contributes to epileptiform activity, which requires the cooperative action of increased synaptic activity.

Original languageEnglish (US)
Pages (from-to)2878-2886
Number of pages9
JournalJournal of neurophysiology
Issue number6
StatePublished - 2001

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