KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias
| Autor: | Michael A. Blanar, Wayne A. Little, Fouad Shalaby, Paul C. Levesque, Wen-Pin Yang, Mary Lee Conder |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Potassium Channels Xenopus Long QT syndrome Molecular Sequence Data Gene Expression Dofetilide Torsades de pointes Biology Pharmacology Internal medicine medicine Animals Humans Amino Acid Sequence KvLQT1 Cloning Molecular Multidisciplinary KCNQ Potassium Channels Heart KCNE3 Clofilium Voltage-gated potassium channel Biological Sciences medicine.disease Potassium channel Endocrinology Potassium Channels Voltage-Gated KCNQ1 Potassium Channel Tachycardia Ventricular biology.protein medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 94:4017-4021 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.94.8.4017 |
| Popis: | 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 I Kr -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 I Ks than other known delayed rectifier K + currents in the heart. |
| Databáze: | OpenAIRE |
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