Acquired dendritic channelopathy in temporal lobe epilepsy.
Inherited channelopathies are at the origin of many neurological disorders. Here we report a form of channelopathy that is acquired in experimental temporal lobe epilepsy (TLE), the most common form of epilepsy in adults. The excitability of CA1 pyramidal neuron dendrites was increased in TLE because of decreased availability of A-type potassium ion channels due to transcriptional (loss of channels) and posttranslational (increased channel phosphorylation by extracellular signal-regulated kinase) mechanisms. Kinase inhibition partly reversed dendritic excitability to control levels. Such acquired channelopathy is likely to amplify neuronal activity and may contribute to the initiation and/or propagation of seizures in TLE.
Bernard
Christophe
C
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. cbernard@inmed.univ-mrs.fr
Anderson
Anne
A
Becker
Albert
A
Poolos
Nicholas P
NP
Beck
Heinz
H
Johnston
Daniel
D
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D010862:Pilocarpine / Q000008:administration & dosage; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; C113580:U 0126; D010862:Pilocarpine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015761:4-Aminopyridine; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases