Functional change of hERG1a mutation H70R on hERG1a homomeric current and hERG1a/1b heteromeric currents

doi:10.3969/j.issn.1006-7795.2022.05.013

Abstract

Abstract: Objective To investigate the electrophysiological effects of hERG1a specific N terminal mutation (H70R) on current (I_Kr) carried by co-expressed hERG1a/1b channels. Methods H70R was introduced in pcDNA3.1 (hERG1a) by site-directed mutagenesis, and transient transfection was applied to express hERG in HEK293 cell. Whole cell patch clamp analysis of the HEK293 cell with expressing wild type and mutant channel was used to investigate the molecular and electrophysiological mechanism. Results H70R showed I_Kr current decrease in both homologues and heterologous hERG channel, the effect on hERG1a/1b channels was more significant than that of hERG1a expressed alone. H70R caused steady-state activation curve to shift to the left and decreased V_1/2 in both homomeric and heteromeric hERG channel. Different from early report, H70R showed no effect on I_Krdeactivation; however, hERG1a/1b channels showed significantly accelerated deactivation. Conclusions hERG1a (H70R) caused a decreased current in both homomeric and heteromeric hERG channel, but a more significant suppression on heteromeric hERG. It suggested that we should pay more attention to the co-expressed I_hERG1a/1b channels in the clinical study of hERG-related channel mutations.

Key words: rapid delayed rectifier potassium channel, Long QT Syndrome, H70R, hERG1a, hERG1b

CLC Number:

R541.7

Feng Li, Yang Jiaxue, Li Xin, Jia Changqi, Jiang Chenxi. Functional change of hERG1a mutation H70R on hERG1a homomeric current and hERG1a/1b heteromeric currents[J]. Journal of Capital Medical University, 2022, 43(5): 747-753.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2022.05.013

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2022/V43/I5/747

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