KCNE3 R53H substitution in familial atrial fibrillation

摘要

Atrial fibrillation (AF) is the most common cardiac arrhythmia with debilitating complications of stroke. Multiple-wavelet re-entry and focal activation from pulmonary vein foci are two dominant electrophysiological theories of AF. Atrial electrical remodeling plays a role in the maintenance of AF. However, molecular mechanisms of the arrhythmia are still poorly understood. The first molecular genetic defect of familial AF has been reported in a Chinese kindred. The locus was mapped to chromosome 11p15.5 by linkage analysis. The mutation was a serine-to-glutamine substitution at position of 140(S140G) in KCNQ1, an alpha subunit of potassium ion channels. The S140G mutation had a gain-of-function effect on the KCNQ1/KCNE1 and KCNQ1/KCNE2 currents, leading to shortening of action potential duration (APD) and effective refractory period ( ERP), a substrate for AF. The loci of chromosome 10q22-24 and chromosome 6q14-16 were identified as linked to familial AF in some patients, but not in others. Familial AF appears to be a genetically heterogeneous disorder.