The sodium channel gene SCN5A and potassium channel genes KCNQ1 and KCNH2 have been widely reported to be genetic risk factors for arrhythmia including Brugada syndrome and long QT syndrome (LQTS).
In this study, we analyzed the genetic variants of KCNQ1, KCNH2, and SCN5A in patients from seven cohorts (total N = 11945, including patients clinically suspected to have inherited arrhythmia [n = 122], other cardiovascular diseases [n = 1045], epilepsy [n = 4797], or other diseases [n = 5841], and healthy controls [n = 140]) who had undergone genetic testing.
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.
In conclusion, short-long RR pattern increased APD dispersion only in LQT2 rabbits through heterogeneous APD restitution and the short-term memory, underscoring the genotype-specific triggering of arrhythmias in LQT syndrome.
Areas covered: The genetic basis for genotyped SQTS variants (SQT1-SQT8) and evidence for arrhythmia substrates from experimental and simulation studies are discussed.
Reduced levels of the cardiac human (h)ERG ion channel protein and the corresponding repolarizing current <i>I</i><sub>Kr</sub> can cause arrhythmia and sudden cardiac death, but the underlying cellular mechanisms controlling hERG surface expression are not well understood.
Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia.
In MI mice, sEHI t-AUCB can repress miR-133, consequently stimulating KCNQ1 and KCNH2 mRNA and protein expression, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmias.
In the 3D wedge, disopyramide and quinidine at clinically-relevant concentrations decreased the dominant frequency of re-entrant excitations and exhibited anti-fibrillatory effects; preventing formation of multiple, chaotic wavelets which developed in SQT1, and could terminate arrhythmias.
The present work uncovered a novel molecular mechanism underlying HERG protein expression and indicated that PML SUMOylation is a critical step in the development of drug-acquired arrhythmia.
We have previously reported that in female rabbits, estrogen increases arrhythmia risk in drug-induced LQTS2 by upregulating L-type Ca<sup>2+</sup> (I<sub>Ca,L</sub>) and sodium-calcium exchange (I<sub>NCX</sub>) currents at the base of the epicardium by a genomic mechanism.
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.
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.
Autoantibodies with beta-adrenergic activity from chronic chagasic patients induce cardiac arrhythmias and early afterdepolarization in a drug-induced LQT2 rabbit hearts.
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.
Patients with KCNE1(G38S) had a rate-dependent repolarization abnormality similar to patients with LQT2 and, therefore, may have a potential risk to develop lethal arrhythmias.
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.
Overexpressing DNAJB14 significantly rescued the defective function of human ether-a-go-go-related gene (hERG) mutant channels associated with long QT syndrome (LQTS), a condition that predisposes to life-threatening arrhythmia, by stabilizing the mutated proteins.
The authors conducted a retrospective study comprising the 606 patients with LQTS (LQT1 in 47%, LQT2 in 34%, and LQT3 in 9%) who were evaluated in Mayo Clinic's Genetic Heart Rhythm Clinic from January 1999 to December 2015.