Differential regulation of HCN channel isoform expression in thalamic neurons of epileptic and non-epileptic rat strains.
Differential regulation of HCN channel isoform expression in thalamic neurons of epileptic and non-epileptic rat strains.
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HCN通道同工型表达在癫痫和非癫痫大鼠菌株的丘脑神经元中的差异调节。
DOI：
10.1016/j.nbd.2011.08.032
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发表时间：
2012-01
影响因子：
6.1
通讯作者：
Budde, Thomas
中科院分区：
文献类型：
--
作者：
Kanyshkova, Tatyana;Meuth, Patrick;Bista, Pawan;Liu, Zhigiang;Ehling, Petra;Caputi, Luigi;Doengi, Michael;Chetkovich, Dane M.;Pape, Hans-Christian;Budde, Thomas
Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels represent the molecular substrate of the hyperpolarization-activated inward current (Ih). Although these channels act as pacemakers for the generation of rhythmic activity in the thalamocortical network during sleep and epilepsy, their developmental profile in the thalamus is not yet fully understood. Here we combined electrophysiological, immunohistochemical, and mathematical modeling techniques to examine HCN gene expression and Ih properties in thalamocortical relay (TC) neurons of the dorsal part of the lateral geniculate nucleus (dLGN) in an epileptic (WAG/Rij) compared to a non-epileptic (ACI) rat strain. Recordings of TC neurons between postnatal day (P) 7 and P90 in both rat strains revealed that Ih was characterized by higher current density, more hyperpolarized voltage dependence, faster activation kinetics, and reduced cAMP-sensitivity in epileptic animals. All four HCN channel isoforms (HCN1–4) were detected in dLGN, and quantitative analyses revealed a developmental increase of protein expression of HCN1, HCN2, and HCN4 but a decrease of HCN3. HCN1 was expressed at higher levels in WAG/Rij rats, a finding that was correlated with increased expression of the interacting proteins filamin A (FilA) and tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b). Analysis of a simplified computer model of the thalamic network revealed that the alterations of Ih found in WAG/Rij rats compensate each other in a way that leaves Ih availability constant, an effect that ensures unaltered cellular burst activity and thalamic oscillations. These data indicate that during postnatal developmental the hyperpolarizing shift in voltage dependency (resulting in less current availability) is compensated by an increase in current density in WAG/Rij thereby possibly limiting the impact of Ih on epileptogenesis. Because HCN3 is expressed higher in young versus older animals, HCN3 likely does not contribute to alterations in Ih in older animals.
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丘脑神经元 HCN 通道异构体的出生后表达模式：与丘脑皮质振荡成熟的关系。
DOI：
10.1523/jneurosci.0689-09.2009
发表时间：
2009-07-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kanyshkova T;Pawlowski M;Meuth P;Dubé C;Bender RA;Brewster AL;Baumann A;Baram TZ;Pape HC;Budde T
通讯作者：
Budde T
影响因子：
3.5
作者：
Broicher, Tilman;Kanyshkova, Tatyana;Budde, Thomas
通讯作者：
Budde, Thomas
影响因子：
2.5
作者：
Destexhe, A;Bal, T;Sejnowski, TJ
通讯作者：
Sejnowski, TJ
影响因子：
5.3
作者：
Brewster, A;Bender, RA;Baram, TZ
通讯作者：
Baram, TZ
DOI：
10.1016/b978-012088554-1/50009-8
发表时间：
2006-01-01
期刊：
MODELS OF SEIZURES AND EPILEPSY
影响因子：
--
作者：
Budde, Thomas;Pape, Hans-Christian;Huguenard, John R.
通讯作者：
Huguenard, John R.