Referenced in: none

Automatically associated channels: Kv1.1 , Kv1.4

Title: The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1.

Authors: Uwe Schulte, Jörg-Oliver Thumfart, Nikolaj Klöcker, Claudia A Sailer, Wolfgang Bildl, Martin Biniossek, Doris Dehn, Thomas Deller, Silke Eble, Karen Abbass, Tanja Wangler, Hans-Günther Knaus, Bernd Fakler

Journal, date & volume: Neuron, 2006 Mar 2 , 49, 697-706

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16504945

Abstract
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.