Rapid loss of dendritic HCN channel expression in hippocampal pyramidal neurons following status epilepticus
| Autor: | Julika Pitsch, Albert J. Becker, Lindsay N. Warner, Nicholas P. Poolos, Sangwook Jung |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Potassium Channels Time Factors Hippocampus Cyclic Nucleotide-Gated Cation Channels Cell Count Status epilepticus Hippocampal formation Epileptogenesis Article Rats Sprague-Dawley Epilepsy Status Epilepticus Channelopathy medicine HCN channel Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Animals Neurons biology Chemistry General Neuroscience Pyramidal Cells Dendrites medicine.disease Potassium channel Rats Gene Expression Regulation biology.protein medicine.symptom Neuroscience |
| Popis: | Epilepsy is associated with loss of expression and function of hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels. Previously, we showed that loss of HCN channel-mediated current (Ih) occurred in the dendrites of CA1 hippocampal pyramidal neurons after pilocarpine-induced status epilepticus (SE), accompanied by loss of HCN1 channel protein expression. However, the precise onset and mechanistic basis of HCN1 channel loss post-SE was unclear, particularly whether it preceded the onset of spontaneous recurrent seizures and could contribute to epileptogenesis or development of the epileptic state. Here, we found that loss ofIhand HCN1 channel expression began within an hour after SE and involved sequential processes of dendritic HCN1 channel internalization, delayed loss of protein expression, and later downregulation of mRNA expression. We also found that anin vitroSE model reproduced the rapid loss of dendriticIh, demonstrating that this phenomenon was not specific toin vivoSE. Together, these results show that HCN1 channelopathy begins rapidly and persists after SE, involves both transcriptional and nontranscriptional mechanisms, and may be an early contributor to epileptogenesis. |
| Databáze: | OpenAIRE |
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