Abstract
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 alpha 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials
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Adolescent
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Adult
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Aged
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Animals
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Atrial Fibrillation / genetics*
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Atrial Fibrillation / physiopathology
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COS Cells
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Child
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China
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Chromosomes, Human, Pair 11 / genetics
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Electrocardiography
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Female
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Haplotypes
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Heart Atria / physiopathology
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Heart Ventricles / physiopathology
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Humans
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KCNQ Potassium Channels
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KCNQ1 Potassium Channel
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Lod Score
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Long QT Syndrome / genetics
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Long QT Syndrome / physiopathology
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Male
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Microsatellite Repeats
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Middle Aged
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Mutation
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Mutation, Missense*
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Myocytes, Cardiac / physiology*
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Patch-Clamp Techniques
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Pedigree
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Potassium Channels / genetics*
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Potassium Channels / physiology
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Potassium Channels, Voltage-Gated*
Substances
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KCNE3 protein, human
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KCNQ Potassium Channels
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KCNQ1 Potassium Channel
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KCNQ1 protein, human
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Potassium Channels
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Potassium Channels, Voltage-Gated
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potassium channel protein I(sk)