RAS BiologyБиофизика Biophysics

  • ISSN (Print) 0006-3029
  • ISSN (Online) 3034-5278

Study of Functional Manifestations of Met23Leu Missense Mutation in the Auxiliary Subunit KCNE2 (Mirp1) of Cardiac Channel Kv11.1

PII
S0006302925010113-1
DOI
10.31857/S0006302925010113
Publication type
Article
Status
Published
Authors
Volume/ Edition
Volume 70 / Issue number 1
Pages
93-103
Abstract
In the present study, we functionally analyzed a missense mutation c.67A>T (p.Met23Leu) in the KCNE2 potassium channel Kv11.1 complementary subunit gene identified in a patient with asymptomatic QT interval prolongation on electrocardiogram. We artificially introduced this substitution into the plasmid encoding the KCNE2 subunit and expressed the mutant gene in Chinese hamster ovary cells together with the wild-type Kv11.1 channel gene to evaluate the effect of the mutation on IK1 current parameters. We used a comprehen-sive approach including the study of the integrated IKr current using the patch-clamp method in a whole-cell configuration in potential fixation mode. The study showed that the c.67A>T mutation (p.Met23Leu) is realized in a gain-of-function type, but the current density carried by Kv11.1 channels is significantly reduced. Fluorescence microscopy showed impaired trafficking of a channel coexpressed with the mutant subunit to the cell surface. We applied molecular modeling to examine the location of the mutant subunit relative to the membrane.
Keywords
потенциал-зависимые калиевые ионные каналы синдром удлиненного интервала QT первичные каналопатии взаимодействие с мембраной
Date of publication
24.10.2025
Year of publication
2025
Number of purchasers
0
Views
21

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