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<p>In the present study, we functionally analyzed the c.67A&gt;T (p.Met23Leu) missense-mutation in the <i>KCNE2</i> gene of potassium channel Kv11.1 complementary subunit identified in a patient with asymptomatic QT interval prolongation on electrocardiogram. We artificially introduced this substitution into the plasmid encoding the <i>KCNE2</i> 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 <i>I</i><sub>KR</sub> current parameters. We used a comprehensive approach including the study of the integrated <i>I</i><sub>Kr</sub> current using whole-cell patch clamp method. The study showed that the c.67A&gt;T mutation (p.Met23Leu) is 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • E. M. Pivovarov,
  • B. Li,
  • A. O. Selin,
  • G. R. Mitrov,
  • G. S. Glukhov,
  • D. V. Abramochkin,
  • M. G. Karlova,
  • A. G. Shestak,
  • V. N. Novoseletsky,
  • E. V. Zaklyazminskaya,
  • K. V. Shaitan,
  • O. S. Sokolova

摘要

In the present study, we functionally analyzed the c.67A>T (p.Met23Leu) missense-mutation in the KCNE2 gene of potassium channel Kv11.1 complementary subunit 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 IKR current parameters. We used a comprehensive approach including the study of the integrated IKr current using whole-cell patch clamp method. The study showed that the c.67A>T mutation (p.Met23Leu) is 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.