DOI: 10.1523/jneurosci.3605-07.2007. Progressive Dendritic HCN Channelopathy during Epileptogenesis in the Rat Pilocarpine Model of Epilepsy

Progressive Dendritic HCN Channelopathy during Epileptogenesis in the Rat Pilocarpine Model of Epilepsy

10.1523/jneurosci.3605-07.2007

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Ion channelopathy plays an important role in human epilepsy with a genetic cause and has been hypothesized to occur in epilepsy after acquired insults to the CNS as well. Acquired alterations of ion channel function occur after induction of status epilepticus (SE) in animal models of epilepsy, but it is unclear how they correlate with the onset of spontaneous seizures. We examined the properties of hyperpolarization-activated cation (HCN) channels in CA1 hippocampal pyramidal neurons in conjunction with video-EEG (VEEG) recordings to monitor the development of spontaneous seizures in the rat pilocarpine model of epilepsy. Our results showed that dendritic HCN channels were significantly downregulated at an acute time point 1 week postpilocarpine, with loss of channel expression and hyperpolarization of voltage-dependent activation. This downregulation progressively increased when epilepsy was established in the chronic period. Surprisingly, VEEG recordings during the acute period showed that a substantial fraction of animals were already experiencing recurrent seizures. Suppression of these seizures with phenobarbital reversed the change in the voltage dependence ofIh, the current produced by HCN channels, but did not affect the loss of HCN channel expression. These results suggest two mechanisms of HCN channel downregulation after SE, one dependent on and one independent of recurrent seizures. This early and progressive downregulation of dendritic HCN channel function increases neuronal excitability and may be associated with both the process of epileptogenesis and maintenance of the epileptic state.

Bibliography

Jung, S., Jones, T. D., Lugo, J. N., Sheerin, A. H., Miller, J. W., DâAmbrosio, R., Anderson, A. E., & Poolos, N. P. (2007). Progressive Dendritic HCN Channelopathy during Epileptogenesis in the Rat Pilocarpine Model of Epilepsy. The Journal of Neuroscience, 27(47), 13012â13021.

Authors 8

Sangwook Jung (first)
Terrance D. Jones (additional)
Joaquin N. Lugo (additional)
Aaron H. Sheerin (additional)
John W. Miller (additional)
Raimondo D'Ambrosio (additional)
Anne E. Anderson (additional)
Nicholas P. Poolos (additional)

References 38 Referenced 194

10.1016/S0920-1211(98)00092-8
10.1126/science.1097065
10.1523/JNEUROSCI.22-11-04591.2002 / J Neurosci / Developmental febrile seizures modulate hippocampal gene expression of hyperpolarization-activated channels in an isoform- and cell-specific manner by Brewster (2002)
10.1038/2661
10.1038/85480
10.1093/brain/awh038
10.1523/JNEUROSCI.2650-05.2005
10.1093/brain/awl018
10.1016/S0306-4522(03)00168-4
10.1038/nn1568
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10.1016/j.expneurol.2007.03.008
10.1097/00001756-200002280-00028 / NeuroReport / Time course of c-FOS expression in status epilepticus induced by amygdaloid stimulation by Hsieh (2000)
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{'key': '2023041303284269000_27.47.13012.18', 'first-page': '713', 'article-title': 'Anticonvulsant drugs: mechanisms of action', 'volume': '44', 'author': 'MacDonald', 'year': '1986', 'journal-title': 'Adv Neurol'} / Adv Neurol / Anticonvulsant drugs: mechanisms of action by MacDonald (1986)
10.1523/JNEUROSCI.18-19-07613.1998 / J Neurosci / Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons by Magee (1998)
10.1038/9158
McNamara JO Huang YZ Leonard AS (2006) Molecular signaling mechanisms underlying epileptogenesis. Sci STKE 2006:re12. (10.1126/stke.3562006re12)
10.1126/science.1124254
10.1523/JNEUROSCI.2877-04.2004
10.1523/JNEUROSCI.19-13-05205.1999 / J Neurosci / Calcium-activated potassium conductances contribute to action potential repolarization at the soma but not the dendrites of hippocampal CA1 pyramidal neurons by Poolos (1999)
10.1038/nn891
10.1523/JNEUROSCI.2069-06.2006
10.1016/0013-4694(72)90177-0
Sakmann B Neher E (1995) in Single-channel recording, Geometric parameters of pipettes and membrane patches, eds Sakmann B Neher E (Plenum, New York), pp 637–650. (10.1007/978-1-4419-1229-9_21)
10.1523/JNEUROSCI.0204-05.2005
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10.1523/JNEUROSCI.22-09-03645.2002 / J Neurosci / Upregulation of a T-type Ca2+ channel causes a long-lasting modification of neuronal firing mode after status epilepticus by Su (2002)
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10.1101/lm.35300
10.1007/s004240050286
10.1111/j.1528-1167.2006.00574.x
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Dates

Type	When
Created	17 years, 9 months ago (Nov. 21, 2007, 1:29 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 2:24 p.m.)
Indexed	2 months ago (July 3, 2025, 12:03 p.m.)
Issued	17 years, 9 months ago (Nov. 21, 2007)
Published	17 years, 9 months ago (Nov. 21, 2007)
Published Online	17 years, 9 months ago (Nov. 21, 2007)
Published Print	17 years, 9 months ago (Nov. 21, 2007)

Funders 0

None

BibTeX

@article{Jung_2007, title={Progressive Dendritic HCN Channelopathy during Epileptogenesis in the Rat Pilocarpine Model of Epilepsy}, volume={27}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.3605-07.2007}, DOI={10.1523/jneurosci.3605-07.2007}, number={47}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Jung, Sangwook and Jones, Terrance D. and Lugo, Joaquin N. and Sheerin, Aaron H. and Miller, John W. and D’Ambrosio, Raimondo and Anderson, Anne E. and Poolos, Nicholas P.}, year={2007}, month=nov, pages={13012–13021} }

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