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http://purl.uniprot.org/citations/30160358http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30160358http://www.w3.org/2000/01/rdf-schema#comment"

Background

Abnormal cardiac ion channels current, including transient outward potassium current (Ito ), is associated with early repolarization syndrome (ERS). Previous studies showed that mutations in SCN1Bβ both to increase the Ito current and to decrease the sodium current. Yet its role in ERS remains unknown.

Objective

To determine the role of mutations in the SCN1Bβ subunits in ERS.

Methods

We screened for mutations in the SCN1B genes from four families with ERS. Wild-type and mutant SCN1Bβ genes were co-expressed with wild-type KCND3 in human embryonic kidney cells (HEK293). Whole-cell patch-clamp technique and co-immunoprecipitation were used to study the electrophysiological properties and explore the underlying mechanisms.

Results

S248R and R250T mutations in SCN1Bβ were detected in 4 families' probands. Neither S248R nor R250T mutation had significant influence on the sodium channel current density (INa ) when co-expressed with SCN5A/WT. Co-expression of KCND3/WT and SCN1Bβ/S248R or SCN1Bβ/R250T increased the transient outward potassium current Ito by 27.44% and 199.89%, respectively (P < 0.05 and P < 0.01, respectively) when compared with SCN1Bβ/WT. Electrophysiological properties showed that S248R and R250T mutations decreased the steady-state inactivation and recovery from inactivation of Ito channel. Co-immunoprecipitation study demonstrated an increased association between SCN1Bβ mutations and Kv4.3 compared with SCN1Bβ/WT (P < 0.05 and P < 0.01, respectively).

Conclusion

The S248R and R250T mutations of SCN1Bβ gene caused gain-of-function of Ito by associated with Kv4.3, which maybe underlie the ERS phenotype of the probands."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.org/dc/terms/identifier"doi:10.1111/jcmm.13839"xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/author"Fan J."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/author"Liu L.J."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/author"Yao H."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/author"Wu S.H."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/author"Zheng Z.H."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/author"Chen X.M."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/author"Cheng Y.J."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/author"Ji C.C."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/name"J Cell Mol Med"xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/pages"5639-5647"xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/title"SCN1Bbeta mutations that affect their association with Kv4.3 underlie early repolarization syndrome."xsd:string
http://purl.uniprot.org/citations/30160358http://purl.uniprot.org/core/volume"22"xsd:string
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