A Defect in the Kv Channel-Interacting Protein 2 (KChIP2) Gene Leads to a Complete Loss of Ito and Confers Susceptibility to Ventricular Tachycardia
Copyright policy )A Defect in the Kv Channel-Interacting Protein 2 (KChIP2) Gene Leads to a Complete Loss of Ito and Confers Susceptibility to Ventricular Tachycardia
KChIP2, a gene encoding three auxiliary subunits of Kv4.2 and Kv4.3, is preferentially expressed in the adult heart, and its expression is downregulated in cardiac hypertrophy. Mice deficient for KChIP2 exhibit normal cardiac structure and function but display a prolonged elevation in the ST segment on the electrocardiogram. The KChIP2(-/-) mice are highly susceptible to the induction of cardiac arrhythmias. Single-cell analysis revealed a substrate for arrhythmogenesis, including a complete absence of transient outward potassium current, I(to), and a marked increase in action potential duration. These studies demonstrate that a defect in KChIP2 is sufficient to confer a marked genetic susceptibility to arrhythmias, establishing a novel genetic pathway for ventricular tachycardia via a loss of the transmural gradient of I(to).
- University of California, San Diego United States
- University of Iowa United States
- University of California, San Diego United States
- University of Calgary Canada
- Institute for Molecular Medicine United States
Mice, Knockout, Patch-Clamp Techniques, Base Sequence, Biochemistry, Genetics and Molecular Biology(all), Myocardium, Calcium-Binding Proteins, Molecular Sequence Data, Action Potentials, Kv Channel-Interacting Proteins, Embryo, Mammalian, Models, Biological, Membrane Potentials, Alternative Splicing, Electrocardiography, Mice, Gene Targeting, Animals, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, In Situ Hybridization
Mice, Knockout, Patch-Clamp Techniques, Base Sequence, Biochemistry, Genetics and Molecular Biology(all), Myocardium, Calcium-Binding Proteins, Molecular Sequence Data, Action Potentials, Kv Channel-Interacting Proteins, Embryo, Mammalian, Models, Biological, Membrane Potentials, Alternative Splicing, Electrocardiography, Mice, Gene Targeting, Animals, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, In Situ Hybridization
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