KCNQ1 Gain-of-Function Mutation in Familial Atrial Fibrillation

Science  10 Jan 2003:
Vol. 299, Issue 5604, pp. 251-254
DOI: 10.1126/science.1077771

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Atrial fibrillation (AF) is a common cardiac arrhythmia whose molecular etiology is poorly understood. We studied a family with hereditary persistent AF and identified the causative mutation (S140G) in the KCNQ1 (KvLQT1) gene on chromosome 11p15.5. The KCNQ1 gene encodes the pore-forming α subunit of the cardiac I Ks channel (KCNQ1/KCNE1), the KCNQ1/KCNE2 and the KCNQ1/KCNE3 potassium channels. Functional analysis of the S140G mutant revealed a gain-of-function effect on the KCNQ1/KCNE1 and the KCNQ1/KCNE2 currents, which contrasts with the dominant negative or loss-of-function effects of the KCNQ1 mutations previously identified in patients with long QT syndrome. Thus, the S140G mutation is likely to initiate and maintain AF by reducing action potential duration and effective refractory period in atrial myocytes.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: drchen{at} (Y.-H.C.); xusj{at} X.)

View Full Text

Cited By...