Isoform-specific dominant-negative effects associated with hERG1 G628S mutation in long QT syndrome.

Mutations in the human ether-a-go-go-related gene 1 (hERG1) cause type 2 long QT syndrome (LQT2). The hERG1 gene encodes a K(+) channel with properties similar to the rapidly activating delayed rectifying K(+) current in the heart. Several hERG1 isoforms with unique structural and functional properties have been identified. To date, the pathogenic mechanisms of LQT2 mutations have been predominantly described in the context of the hERG1a isoform. In the present study, we investigated the functional consequences of the LQT2 mutation G628S in the hERG1b and hERG1a(USO) isoforms.

Pubmed ID: 22876326