Seizure susceptibility is associated with altered protein expression of voltage-gated calcium channel subunits in inferior colliculus neurons of the genetically epilepsy-prone rat.
Seizure susceptibility is associated with altered protein expression of voltage-gated calcium channel subunits in inferior colliculus neurons of the genetically epilepsy-prone rat.
复制标题
DOI：
10.1016/j.brainres.2009.10.019
复制
发表时间：
2010-01-13
期刊：
影响因子：
2.9
通讯作者：
Faingold, Carl L.
中科院分区：
文献类型：
--
作者：
N'Gouemo, Prosper;Yasuda, Robert;Faingold, Carl L.
下丘（IC）是遗传性癫痫易感大鼠（GEPR）癫痫发作的公认部位。我们之前报道了高阈值电压激活（HVA）钙（Ca2+）通道的电流密度在GEPR-3（中度癫痫发作严重亚株）的IC神经元中显着增强。本研究探讨了在钙离子电流密度增强的IC神经元中，HVA Ca2+通道的亚基蛋白水平是否发生改变。定量结果显示，与SD大鼠相比，癫痫发作初期的GEPR-3s (SN-GEPR-3s) IC神经元中Ca2+通道成孔α1D （l型）和α1E亚基（r型）的蛋白表达水平显著升高。与对照SD大鼠相比，SN-GEPR-3s的IC神经元中Ca2+通道调节β3和α2δ亚基的蛋白表达水平分别显著升高和降低。与对照SD大鼠相比，SN-GEPR-3s IC神经元中Ca2+通道成孔α1A （P/ q型）、α1B （n型）和α1C （l型）亚基的蛋白表达未发生变化。单次癫痫发作选择性地增强了GEPR-3s IC神经元中Ca2+通道α1A亚基的蛋白表达。因此，Ca2+通道α1D和α1E亚基的上调可能是GEPR IC神经元中L-型和r型HVA Ca2+通道电流密度增强的分子机制，并可能是其癫痫易感性增强的遗传基础。癫痫发作引起的Ca2+通道α1A亚基的上调可能有助于GEPR中重复性癫痫发作引起的IC神经元兴奋性增加。
The inferior colliculus (IC) is the consensus site for seizure initiation in the genetically epilepsy-prone rat (GEPR). We have previously reported that the current density of high threshold voltage-activated (HVA) calcium (Ca2+) channels was markedly enhanced in IC neurons of the GEPR-3 (moderate seizure severity substrain of the GEPR). The present study examines whether subunit protein levels of HVA Ca2+ channels are altered in IC neurons that exhibit enhanced Ca2+ current density. Quantification shows that the levels of protein expression of the Ca2+ channel pore-forming α1D (L-type) and α1E subunits (R-type), were significantly increased in IC neurons of seizure-naive GEPR-3s (SN-GEPR-3s) compared to control Sprague-Dawley (SD) rats. Significant increases and decreases in the levels of protein expression of Ca2+ channel regulatory β3 and α2δ subunits occurred in IC neurons of SN-GEPR-3s compared to control SD rats, respectively. No changes occurred in the protein expression of Ca2+ channel pore-forming α1A (P/Q-type), α1B (N-type) and α1C (L-type) subunits in IC neurons of SN-GEPR-3s compared to control SD rats. A single seizure selectively enhanced protein expression of Ca2+ channel α1A subunits in IC neurons of GEPR-3s. Thus, up-regulation of Ca2+ channel α1D and α1E subunits may represent the molecular mechanisms for the enhanced current density of L- and R-type of HVA Ca2+ channels in IC neurons of the GEPR, and may contribute to the genetic basis of their enhanced seizure susceptibility. The up-regulation of Ca2+ channel α1A subunits induced by seizures may contribute to the increasing IC neuronal excitability that results from repetitive seizures in the GEPR.
登录
查看更多内容
影响因子：
11.2
作者：
Berkovic, SF;Howell, RA;Hopper, JL
通讯作者：
Hopper, JL
影响因子：
6.1
作者：
BROWNING, RA
通讯作者：
BROWNING, RA
DOI：
10.1016/0306-3623(90)91032-m
发表时间：
1990-01-01
期刊：
GENERAL PHARMACOLOGY-THE VASCULAR SYSTEM
影响因子：
--
作者：
DESARRO, G;DESARRO, A;MELDRUM, BS
通讯作者：
MELDRUM, BS
DOI：
10.1073/pnas.76.9.4350
发表时间：
1979-01-01
影响因子：
11.1
作者：
TOWBIN, H;STAEHELIN, T;GORDON, J
通讯作者：
GORDON, J
影响因子：
5.3
作者：
FAINGOLD, CL;GEHLBACH, G;CASPARY, DM
通讯作者：
CASPARY, DM