Autosomal dominant epilepsy with auditory features results from mutations in leucine-rich glioma-inactivated 1 (LGI1), a soluble glycoprotein secreted by neurons. Animal models of LGI1 depletion display spontaneous seizures, however, the function of LGI1 and the mechanisms by which deficiency leads to epilepsy are unknown. We investigated the effects of pure recombinant LGI1 and genetic depletion on intrinsic excitability, in the absence of synaptic input, in hippocampal CA3 neurons, a classical focus for epileptogenesis. Our data indicate that LGI1 is expressed at the axonal initial segment and regulates action potential firing by setting the density of the axonal Kv1.1 channels that underlie dendrotoxin-sensitive D-type potassium current. LGI1 deficiency incurs a >50% down-regulation of the expression of Kv1.1 and Kv1.2 via a posttranscriptional mechanism, resulting in a reduction in the capacity of axonal D-type current to limit glutamate release, thus contributing to epileptogenesis.
Pubmed ID: 28673977 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Ankyrin-G (Staining)
View all literature mentionsThis unknown targets ADAM23
View all literature mentionsThis monoclonal targets HCN4 ion channel
View all literature mentionsThis monoclonal targets Pan-Kvbeta K+ channel
View all literature mentionsThis monoclonal targets ADAM22 (extracellular)
View all literature mentionsThis monoclonal targets Kv1.2 K+ channel
View all literature mentionsThis monoclonal targets Kv1.1 K+ channel (external)
View all literature mentionsThis monoclonal targets Lgi1
View all literature mentionsThis polyclonal targets Lgi1
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsA user-friendly convenient toolkit to calculate Functional Connectivity (FC), Regional Homogeneity (ReHo), Amplitude of Low-Frequency Fluctuation (ALFF), Fractional ALFF (fALFF), Gragner causality and perform statistical analysis. You also can use REST to view your data, perform Monte Carlo simulation similar to AlphaSim in AFNI, calculate your images, regress out covariates, extract Region of Interest (ROI) time courses, reslice images, and sort DICOM files.
View all literature mentionsCell line Sf9 is a Spontaneously immortalized cell line with a species of origin Spodoptera frugiperda
View all literature mentions