Endoplasmic reticulum retention of KCNQ2 potassium channel mutants following temperature elevation

Issue title: Selected papers from the 6th China–France International Symposium “Stem Cells and Regenerative Medicine” and the first meeting of the France–China International CNRS Network (GDRI) CeSMeR, Nancy, 10–13 July 2016

Guest editors: J.-F. Stoltz, J. Magdalou and D. Bensoussan

Article type: Research Article

Authors: Yu, Fang^{a; *; **} | Xu, Jian^{b; *} | Xiao, Zheman^c | Peng, Biwen^c | He, Xiaohua^c

Affiliations: [a] Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China | [b] Weifang Maternity and Child Hospital, Weifang, China | [c] Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, China

Correspondence: [**] Corresponding author: Fang Yu, Donghu Road #169, Wuchang, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China. Tel.: +86-27-67813043; Fax: +86-27-67813043; E-mail: fang-yu@whu.edu.cn.

Note: [*] These authors contributed equally to this work.

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.

Keywords: KCNQ2, ion channels, temperature, febrile seizures, benign familial neonatal convulsions

DOI: 10.3233/BME-171647

Journal: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S243-S253, 2017