Schulte Uwe, Thumfart Jörg-Oliver, Klöcker Nikolaj, Sailer Claudia A, Bildl Wolfgang, Biniossek Martin, Dehn Doris, Deller Thomas, Eble Silke, Abbass Karen, Wangler Tanja, Knaus Hans-Günther, Fakler Bernd
Logopharm GmbH, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
Neuron. 2006 Mar 2;49(5):697-706. doi: 10.1016/j.neuron.2006.01.033.
The voltage-gated potassium (Kv) channel subunit Kv1.1 is a major constituent of presynaptic A-type channels that modulate synaptic transmission in CNS neurons. Here, we show that Kv1.1-containing channels are complexed with Lgi1, the functionally unassigned product of the leucine-rich glioma inactivated gene 1 (LGI1), which is causative for an autosomal dominant form of lateral temporal lobe epilepsy (ADLTE). In the hippocampal formation, both Kv1.1 and Lgi1 are coassembled with Kv1.4 and Kvbeta1 in axonal terminals. In A-type channels composed of these subunits, Lgi1 selectively prevents N-type inactivation mediated by the Kvbeta1 subunit. In contrast, defective Lgi1 molecules identified in ADLTE patients fail to exert this effect resulting in channels with rapid inactivation kinetics. The results establish Lgi1 as a novel subunit of Kv1.1-associated protein complexes and suggest that changes in inactivation gating of presynaptic A-type channels may promote epileptic activity.
电压门控钾离子（Kv）通道亚基Kv1.1是突触前A型通道的主要组成部分，可调节中枢神经系统神经元的突触传递。在此，我们表明，含有Kv1.1的通道与富含亮氨酸的胶质瘤失活基因1（LGI1）的功能未明确产物Lgi1复合，LGI1是常染色体显性外侧颞叶癫痫（ADLTE）的病因。在海马结构中，Kv1.1和Lgi1均与Kv1.4和Kvbeta1在轴突终末共同组装。在由这些亚基组成的A型通道中，Lgi1选择性地阻止由Kvbeta1亚基介导的N型失活。相反，在ADLTE患者中鉴定出的缺陷Lgi1分子无法发挥这种作用，导致通道具有快速失活动力学。这些结果确立了Lgi1作为Kv1.1相关蛋白复合物的新型亚基，并表明突触前A型通道失活门控的变化可能促进癫痫活动。
