KvLQT1, a Voltage-Gated Potassium Channel Responsible for Human Cardiac Arrhythmias

The clinical features of long QT syndrome result from episodic life-threatening cardiac arrhythmias, specifically the polymorphic ventricular tachycardia torsades de pointes. KVLQT1 has been established as the human chromosome 11-linked gene responsible for more than 50% of inherited long QT syndrom...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1997-04, Vol.94 (8), p.4017-4021
Main Authors: Yang, Wen-Pin, Levesque, Paul C., Little, Wayne A., Conder, Mary Lee, Shalaby, Fouad Y., Blanar, Michael A.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino acids
Animals
Biological Sciences
Cardiac arrhythmia
Cloning
Cloning, Molecular
Complementary DNA
Complementary RNA
Deoxyribonucleic acid
DNA
DNA probes
Electric current
Electric potential
Gene Expression
Genes
Heart - physiopathology
HEK293 cells
Humans
KCNQ Potassium Channels
KCNQ1 Potassium Channel
Messenger RNA
Molecular Sequence Data
Oocytes
Pharmacology
Potassium
Potassium Channels - isolation & purification
Potassium Channels - physiology
Potassium Channels, Voltage-Gated
Tachycardia, Ventricular - physiopathology
Xenopus
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Summary:The clinical features of long QT syndrome result from episodic life-threatening cardiac arrhythmias, specifically the polymorphic ventricular tachycardia torsades de pointes. KVLQT1 has been established as the human chromosome 11-linked gene responsible for more than 50% of inherited long QT syndrome. Here we describe the cloning of a full-length KVLQT1 cDNA and its functional expression. KVLQT1 encodes a 676-amino acid polypeptide with structural characteristics similar to voltage-gated potassium channels. Expression of KvLQT1 in Xenopus oocytes and in human embryonic kidney cells elicits a rapidly activating, K+-selective outward current. The IKr-specific blockers, E-4031 and dofetilide, do not inhibit KvLQT1, whereas clofilium, a class III antiarrhythmic agent with the propensity to induce torsades de pointes, substantially inhibits the current. Elevation of cAMP levels in oocytes nearly doubles the amplitude of KvLQT1 currents. Coexpression of minK with KvLQT1 results in a conductance with pharmacological and biophysical properties more similar to IKsthan other known delayed rectifier K+currents in the heart.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.94.8.4017