| BackgroundAtrial fibrillation (AF) is a common clinic rhythmus disorder that brings serious complications such as heart failure and embolism. The clinical management for AF includes rate or rhythm control and anticoagulation. The outcome, however, is still not acceptable in some of the patients. The mechanism of AF has been intensively investigated in recent two decades both in clinic and in electrophysiological laboratory, the molecular nature of AF, on the other hand is poorly understood. Recent studies imply that it may be related to genetic abnormality of potassium channels. Chen and co-workers found that S140G mutation of KCNQ1 (KvLQTl) gene on chromosome 11p15.5 accounted for hereditary AF in a Chinese family. Later they found that KCNE2 R27C mutation caused AF in another family. Lai et al. reported that KCNE1 (minK) gene 38G allele was linked to patients with AF phenotype.KCNQ1 and KCNE1 encode α and β subunits of slow delayed rectifier potassium current (IKs) channel in human heart. S140G mutation of KCNQ1 results in "gain of function" of IKs, which may lead to acceleration of repolarization of action potential and shortening of refractory period of atrium myocytes and thus facilitate the development and sustainment of AF according to Moe's multiple reentrant wavelets theory. The observation that azimilide, a highly selective blocker of IKs, is superior to dofetilide, a rapid delayed rectifier potassium current (IKr) blocker, in terminating experimental AF supported the hypothesis.The KCNE gene family codes small, single transmembrane domain peptides that associate with pore-forming potassium channel subunits to form mixed complexes with unique characteristics. There are five types of KCNE genes. KCNE1 and KCNE2 encode the β subunits of IKs and IKr channels. KCNE3 is seldom expressed in the heart and KCNE5 is located in X chromosome. The human KCNE4 gene has been cloned recently in our institute and it could slow the activation of IKs... |
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