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Updated: Jul 11, 2026
11:33
Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
Published on: March 12, 2013
Differential association between HERG and KCNE1 or KCNE2
Sung Yon Um1, Thomas V McDonald
1Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Plos One
|September 27, 2007
Summary
HERG channel assembly preferentially involves KCNE1 over KCNE2 due to distinct protein trafficking and cellular retention mechanisms, influencing final channel composition.
Area of Science:
- Molecular biology
- Cell biology
- Ion channel biophysics
Background:
- KCNE1 and KCNE2 are small proteins proposed as accessory subunits for the HERG (Human Ether-à-go-go-Related Gene) channel.
- Understanding the cell biology of KCNE-HERG interactions is crucial for elucidating cardiac ion channel function.
Purpose of the Study:
- To investigate the cell biology of the interaction between KCNE1, KCNE2, and the HERG channel.
- To determine how KCNE subunits affect HERG channel trafficking and assembly.
Main Methods:
- Co-expression of KCNE1, KCNE2, and HERG in a cellular system.
- Co-precipitation assays to assess protein interactions.
- Brefeldin A treatment and ER-retention signal engineering to study protein trafficking.
- Confocal immunofluorescence and surface labeling to analyze protein localization.
- Analysis of extracellular media for secreted proteins.
Main Results:
- KCNE1 co-precipitated more readily with HERG than KCNE2.
- Blocking forward protein trafficking increased intracellular KCNE2 abundance and its association with HERG relative to KCNE1.
- HERG co-localized more completely with KCNE1 than KCNE2 across cellular compartments (ER, Golgi, plasma membrane).
- KCNE2 was more abundant at the cell surface and also found extracellularly, while KCNE1 showed greater co-localization with the ER marker calnexin.
Conclusions:
- Differential trafficking rates and cellular retention, rather than affinity, dictate HERG's preferential assembly with KCNE1 during biogenesis.
- The final in vivo channel subunit composition is likely determined by cell-specific expression levels and distinct protein processing/trafficking of KCNE subunits.
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