Structural Effects of an LQT-3 Mutation on Heart Na+ Channel Gating
نویسندگان
چکیده
منابع مشابه
Structural effects of an LQT-3 mutation on heart Na+ channel gating.
Computational methods that predict three-dimensional structures from amino acid sequences have become increasingly accurate and have provided insights into structure-function relationships for proteins in the absence of structural data. However, the accuracy of computational structural models requires experimental approaches for validation. Here we report direct testing of the predictions of a ...
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Background—D1790G, a mutation of SCN5A, the gene that encodes the human Na channel a-subunit, is linked to 1 form of the congenital long-QT syndrome (LQT-3). In contrast to other LQT-3–linked SCN5A mutations, D1790G does not promote sustained Na channel activity but instead alters the kinetics and voltage-dependence of the inactivated state. Methods and Results—We modeled the cardiac ventricula...
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Congenital long QT syndrome is a rare disease in which the electrocardiogram QT interval is prolonged due to dysfunctional ventricular repolarization. Variant 3 (LQT-3) is associated with mutations in SCN5A, the gene coding for the heart Na(+) channel alpha subunit. Arrhythmias in LQT-3 mutation carriers are more likely to occur at rest, when heart rate is slow. Several LQT-3 Na(+) channel muta...
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Ca channel subunits are important molecular determinants of the kinetics and voltage dependence of Ca channel gating. Through direct interactions with channel-forming 1 subunits, subunits enhance expression levels, accelerate activation, and have variable effects on inactivation. Four distinct subunit genes each encode five homologous sequence domains (D1–5), three of which (D1, D3, and D5) und...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2004
ISSN: 0006-3495
DOI: 10.1016/s0006-3495(04)74251-4