Referenced in: none

Automatically associated channels: Kir1.1 , Kir4.1 , Kir5.1

Title: Variable loss of Kir4.1 channel function in SeSAME syndrome mutations.

Authors: Xiaofang Tang, Darwin Hang, Andrea Sand, Paulo Kofuji

Journal, date & volume: Biochem. Biophys. Res. Commun., 2010 Sep 3 , 399, 537-41

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20678478

Abstract
SeSAME syndrome is a complex disease characterized by seizures, sensorineural deafness, ataxia, mental retardation and electrolyte imbalance. Mutations in the inwardly rectifying potassium channel Kir4.1 (KCNJ10 gene) have been linked to this condition. Kir4.1 channels are weakly rectifying channels expressed in glia, kidney, cochlea and possibly other tissues. We determined the electrophysiological properties of SeSAME mutant channels after expression in transfected mammalian cells. We found that a majority of mutations (R297C, C140R, R199X, T164I) resulted in complete loss of Kir4.1 channel function while two mutations (R65P and A167V) produced partial loss of function. All mutant channels were rescued upon co-transfection of wild-type Kir4.1 but not Kir5.1 channels. Cell-surface biotinylation assays indicate significant plasma membrane expression of all mutant channels with exception of the non-sense mutant R199X. These results indicate the differential loss of Kir channel function among SeSAME syndrome mutations.