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  • Vinculin variant M94I identified in sudden unexplained nocturnal death syndrome decreases cardiac sodium current.

Vinculin variant M94I identified in sudden unexplained nocturnal death syndrome decreases cardiac sodium current.

Scientific reports (2017-02-22)
Jianding Cheng, John W Kyle, Brandi Wiedmeyer, Di Lang, Ravi Vaidyanathan, Jonathan C Makielski
ABSTRACT

Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative disorder with unclear etiology. Vinculin (VCL) was linked to sudden arrhythmia death in VCL knockout mice prior to the appearance of cardiomyopathy. We hypothesized VCL mutations underlie risk for SUNDS. A rare heterozygous variant VCL-M94I was found in a SUNDS victim who suffered sudden nocturnal tachypnea and lacked pathogenic variants in known arrhythmia-causing genes. VCL was identified to interact with SCN5A in vitro/vivo. The VCL-M94I was co-expressed with the cardiac sodium channel in HEK293 cells and also overexpressed in induced pluripotent stem cells derived cardiomyocytes (iPSCs-CM). In HEK293 cells with pH 7.4, VCL-M94I caused ~30% decrease in peak sodium current (I

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-SCN5A antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-Vinculin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution