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 language | English |
---|---|
Pages (from-to) | 15240-15253 |
Number of pages | 14 |
Journal | Journal of Neuroscience |
Volume | 35 |
Issue number | 46 |
DOIs | |
State | Published - 18 Nov 2015 |
Bibliographical note
Publisher Copyright:© 2015 the authors.
Keywords
- Epilepsy
- Persistent sodium current
- Polyamines
- Sodium channels
- Spermine
- Synaptic integration