title: Endoplasmic reticulum retention of KCNQ2 potassium channel mutants following temperature elevation.
abstract: BACKGROUND
  KCNQ2 plays a key role in the regulation of neuronal excitability. The R214W and Y284C mutants of KCNQ2 channels, which are associated with BFNC, can decrease channel function to cause neuronal hyperexcitability and promote seizures. Previous studies revealed that elevated temperature caused up-regulation of KCNQ2 expression.
  
  
  OBJECTIVE
  The present study sought to investigate the impact of temperature elevation on neuronal KCNQ2 ion channel mutants.
  
  
  METHODS
  Protein expression of wt KCNQ2 and the R214W, Y284C and truncated selective filter mutants at different temperatures was detected by live-cell confocal fluorescence microscopy and by Western blotting. Whole-cell patch clamp was performed to record the effect of temperature on the electrophysiological activity of KCNQ2 channels.
  
  
  RESULTS
  Temperature elevation caused an unexpected increase in voltage-dependent KCNQ2 channel activation but also increased the endoplasmic reticulum (ER) retention of KCNQ2 protein, and the ER retention was greater for mutants associated with BFNC than for wt KCNQ2. Temperature elevation did not increase the fluorescence intensity of cells transfected with a truncated selective filter mutant.
  
  
  CONCLUSIONS
  The direct effect of heat on KCNQ2 channels may be involved in excitability regulation of neurons, and the P-loop region is critical for temperature-dependent modulation of the expression and trafficking of KCNQ2 channels.
authors.affiliation: Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: Weifang Maternity and Child Hospital, Weifang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, China.
authors.forename: Zheman
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, China.
authors.forename: Biwen
authors.initials: B
authors.lastname: Peng
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
mesh_terms: D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006358:Hot Temperature; D006801:Humans; D051658:KCNQ2 Potassium Channel / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D021381:Protein Transport; D013696:Temperature
chemical_list: D051658:KCNQ2 Potassium Channel
keywords: KCNQ2; benign familial neonatal convulsions; febrile seizures; ion channels; temperature