Long-QT syndrome type-2 (LQT2) is characterized by reduced functional expression of the human ether-à-go-go related (hERG) gene product, resulting in impaired cardiac repolarization and predisposition to fatal arrhythmia.
Human ether-a-go-go-related gene (hERG; K<sub>v</sub> 11.1) channel inhibition is a widely accepted predictor of cardiac arrhythmia. hERG channel inhibition alone is often insufficient to predict pro-arrhythmic drug effects.
A common over-the-counter (OTC) non-opioid antitussive drug, clobutinol, was recently withdrawn from the market due to its potential to induce cardiac arrhythmias by a blockade of the potassium channel coded by the human ether-à-go-go-related gene (hERG).
A likely mechanism for QT interval prolongation and TdP arrhythmias is blockade of the rapid component of the cardiac delayed rectifier K+ current (IKr), which is encoded by human ether-a-go-go-related gene (HERG).
A novel heterozygous missense mutation in exon 7 of KCNH2 gene, causing a protein change p.F617V, was found in a family with life-threatening arrhythmias in women and clinical outcome typical for long QT2 syndrome.
Although we were unable to test for inducibility of arrhythmia susceptibility due to lack of patients' consent, our computer simulations predict a steeper steady-state restitution curve for the D172N and WT/D172N mutation, compared with WT or to HERG or KvLQT1 mutations, which may predispose SQT3 patients to a greater risk of reentrant arrhythmias.
Analysis of the biophysics and molecular pharmacology of ion channels expressed in cardiomyocytes (CMs) differentiated from these iPSCs (iPSC-CMs) demonstrates a primary LQT-3 (Na(+) channel) defect responsible for the arrhythmias not influenced by the KCNH2 polymorphism.
Areas covered: The genetic basis for genotyped SQTS variants (SQT1-SQT8) and evidence for arrhythmia substrates from experimental and simulation studies are discussed.
Autoantibodies with beta-adrenergic activity from chronic chagasic patients induce cardiac arrhythmias and early afterdepolarization in a drug-induced LQT2 rabbit hearts.
Blockage of some ion channels and in particular, the hERG (human Ether-a'-go-go-Related Gene) cardiac potassium channel delays cardiac repolarization and can induce arrhythmia.
Congenital mutations in the cardiac Kv11.1 channel can cause long QT syndrome type 2 (LQTS2), a heart rhythm disorder associated with sudden cardiac death.
Defective functional PM expression of the human ether-a-go-go-related gene (hERG) K(+) channel leads to the prolongation of the ventricular action potential that causes long QT syndrome 2 (LQT2), with increased propensity for arrhythmia and sudden cardiac arrest.
Electrophysiological analysis of patient-derived LQT2 hiPSC cardiomyocytes treated with mutation-specific siRNAs showed normalized action potential durations (APDs) and K(+) currents with the concurrent rescue of spontaneous and drug-induced arrhythmias (presented as early-afterdepolarizations).
Finally, three potentially proarrhythmic factors characteristic of ischemia were identified: pH decrease; oxygen free radicals, which both increase the flow of K(+) ions through human ether-a-go-go-related gene and hK(v)1.5, producing a reduction in action potential duration, frequently leading to cardiac arrhythmias; and lysophosphatidylcholine, a metabolite involved in the production of cardiac arrhythmias early during ischemia that was shown to be a major cause of electrical uncoupling.
Genetic mutations in KCNH2, which encodes hERG, the alpha subunit of the potassium channel responsible for the I<sub>Kr</sub> current, cause long QT syndrome (LQTS), an inherited cardiac arrhythmia disorder.
Identification and characterization of a compound that protects cardiac tissue from human Ether-à-go-go-related gene (hERG)-related drug-induced arrhythmias.
Identification of mutations in the human-ether-a-go-go-related gene (HERG) K(+) channel as the molecular basis of congenital long QT syndrome type 2 also led to the discovery that HERG is the molecular target for the vast majority of drugs (both cardiac and non-cardiac) that cause drug-induced arrhythmias.
Impaired functional plasma membrane (PM) expression of the hERG K<sup>+</sup>-channel is associated with Long-QT syndrome type-2 (LQT2) and increased risk of cardiac arrhythmia.