Downregulation of spermine augments dendritic persistent sodium currents and synaptic integration after status epilepticus

Michel Royeck, Tony Kelly, Thoralf Opitz, David Marian Otte, Andreas Rennhack, Anne Woitecki, Julika Pitsch, Albert Becker, Susanne Schoch, Ulrich Benjamin Kaupp, Yoel Yaari, Andreas Zimmer, Heinz Beck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Dendritic voltage-gated ion channels profoundly shape the integrative properties of neuronal dendrites. In epilepsy, numerous changes in dendritic ion channels have been described, all of them due to either their altered transcription or phosphorylation. In pilocarpinetreated chronically epileptic rats, we describe a novel mechanism that causes an increased proximal dendritic persistent Na+ current (INaP).Wedemonstrate using a combination of electrophysiology and molecular approaches that the upregulation of dendritic INaP is due to a relief from polyamine-dependent inhibition. The polyamine deficit in hippocampal neurons is likely caused by an upregulation of the degrading enzyme spermidine/spermine acetyltransferase. Multiphoton glutamate uncaging experiments revealed that the increase in dendritic INaP causes augmented dendritic summation of excitatory inputs. These results establish a novel post-transcriptional modification of ion channels in chronic epilepsy and may provide a novel avenue for treatment of temporal lobe epilepsy.

Original languageEnglish
Pages (from-to)15240-15253
Number of pages14
JournalJournal of Neuroscience
Volume35
Issue number46
DOIs
StatePublished - 18 Nov 2015

Bibliographical note

Publisher Copyright:
© 2015 the authors.

Keywords

  • Epilepsy
  • Persistent sodium current
  • Polyamines
  • Sodium channels
  • Spermine
  • Synaptic integration

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