Short QT Syndrome: From Bench to Bedside

KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia

“…This article is a PNAS Direct Submission. 1 To whom correspondence should be addressed. E-mail: jjalife@umich.edu.…”

“…cellular electrophysiology | computer models | genetics | ion channels | channelopathies T he short QT syndrome (SQTS) is an inherited arrhythmogenic disorder characterized by a remarkably abbreviated repolarization and a predisposition to supraventricular and ventricular arrhythmias in the absence of detectable structural heart disease (1). Mutations found in SQTS patients in the genes encoding potassium channels cause "gain of function," whereas mutations found in the alpha 1C subunit of the voltage-dependent L-type Ca + channel (CACNA1C), the beta 2b subunit of the voltage dependent Ca 2+ channel (CACNB2B) and the alpha2/delta subunit 1 of the voltage dependent Ca 2+ channel (CACNA2D1) cause "loss of function" (1,2). In 2005, we reported a mutation (D172N) in the strong inward rectifier K + channel protein (Kir2.1), which is coded by KCNJ2, in an SQTS patient: Functional characterization revealed that D172N shows an increased outward component of the inward rectifier current I K1 (3).…”

The Serum- and Glucocorticoid-inducible Kinases SGK1 and SGK3 Regulate hERG Channel Expression via Ubiquitin Ligase Nedd4-2 and GTPase Rab11

“…For example, it has been reported that psychosocial stress plays a role in otherwise unexplained cardiac arrest (39). Furthermore, a gain-of-function SGK1 mutation has been reported in twins who displayed the shortened QT interval, which induces arrhythmias and sudden death (40,41).…”

<b>Profile of the cardiac repolarization in cervical spinal cord injury subjects performing physical exercise

“…However, QTc interval shorter than 350 ms may also be a predictor of heart failure, ventricular tachycardia, ventricular fibrillation and syncope (Patel, Yan, & Antzelevitch, 2010;Viskin, 2009). Some studies showed that cervical SCI promote shortening of QT interval and increases in QT dispersion (Bartholdy et al, 2014;Saunders et al, 2015).The short QT interval shows uniformity in time and space in the ventricle, producing an exaggerated heterogeneity of repolarization, hastens recovery and reduced refractoriness in the ventricle (Patel et al, 2010).The ion channelopathies that cause SQTS (mutation in KCNH2, KCNQ1, KCNJ2 that encodes cardiac K + channel or mutation in CACNA1c, CACNB2b that encodes cardiac Ca 2+ channel) not only abbreviate repolarization but they significantly increase dispersion of repolarization, thus creating the cellular basis for both the substrate and trigger necessary for the initiation of reentry (Patel et al, 2010). Rodenbaugh and colleagues (Rodenbaugh, Collins, Nowacek, & DiCarlo, 2003) observed that paraplegic rats showed high susceptibility to ventricular tachyarrhythmias via altering cardiac function and an abundance of Ca 2+ regulatory proteins.…”