AI Article Synopsis
- Recent research indicates that mutations in the KCNE1 gene, which encodes a β-subunit of cardiac potassium channels, are linked to ventricular fibrillation and might also play a role in early repolarization syndrome (ERS), although this connection is not fully understood.
- The study aimed to investigate the association of the KCNE1 mutation, specifically S38G, with ERS by analyzing genomic data from four families and performing various functional tests in a laboratory setting.
- Findings revealed that the S38G mutation resulted in reduced protein expression and impaired membrane trafficking of KCNE1, leading to decreased electrical currents, suggesting that KCNE1 could be a significant gene involved in the modulation of early repolarization syndrome.
Article Abstract
Background: Recent studies have revealed that mutation in KCNE1, β-subunits of cardiac potassium channel, involved in ventricular fibrillation. Whereas its role in early repolarization syndrome (ERS) is less well understood.
Objective: To study whether mutant in KCNE1 is associated with ERS and explore the possible underlying molecular mechanisms.
Methods: Whole genome from four unrelated families with ERS was amplified and sequenced. Wild-type (WT) KCNE1 and/or KCNE1-S38G (S38G) were expressed in HEK293 cells with KCNQ1. Functional studies included whole-cell patch-clamp, western blot and immunofluorescence were performed to reveal the possible underlying mechanisms.
Results: The co-expression of KCNE1-S38G and KCNQ1 decreased tail current density of I but had little effect in modulation channel kinetics of I. Compared with KCNE1-WT, the expression and membrane location of KCNE1-S38G decreased. Co-expression of KCNE1-WT and KCNE1-S38G partially rescued the function of I channel.
Conclusions: The S38G mutation induced a loss-of-function of I due to decreasing of KCNE1 protein expression and defecting in KCNE1 protein membrane trafficking. Our findings suggested that KCNE1 may be one of the possible modulatory genes associated to ERS.
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| http://dx.doi.org/10.1016/j.yexcr.2018.01.030 | DOI Listing |
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