Cardiac Delayed Rectifier Potassium Channels in Health and Disease

Chen, Lei; Sampson, Kevin J.; Kass, Robert S.

doi:10.1016/j.ccep.2016.01.004

Cited by 54 publications

(38 citation statements)

References 182 publications

(179 reference statements)

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“…K V 7.1 consists of four α-subunits which co-assemble with KCNE1 β-subunits to generate the I Ks current. The KCNQ1 α-subunit has a voltage sensing domain (S1–4), a pore forming domain (S5–6), as well as intracellular N- and C-termini [8]. LQT1 manifests on the surface electrocardiogram as a broad-based and symmetrical T-wave with a prolonged QTc interval [9].…”

Section: Genetics Of Lqtsmentioning

confidence: 99%

“…hERG (human Ether-à-go-go -Related Gene) or KCNH2 codes for the voltage-gated pore forming α-subunit of the inwardly rectifying potassium channel subunit K V 11.1. The KCNH2 α-subunits form a complex with KCNE2 , a single transmembrane protein homologous to KCNE1 , to generate the I Kr current, intimately involved in membrane repolarization [8]. Heterozygote KCNH2 mutations exert a dominant-negative effect on wild-type hERG channel-associated I Kr currents by impairing trafficking pathways or altered channel kinetics of the resulting co-assembled hERG heterotetramers [15].…”

Section: Genetics Of Lqtsmentioning

confidence: 99%

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Long QT Syndrome: Genetics and Future Perspective

et al. 2019

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Long QT syndrome (LQTS) is an inherited primary arrhythmia syndrome that may present with malignant arrhythmia and, rarely, risk of sudden death. The clinical symptoms include palpitations, syncope, and anoxic seizures secondary to ventricular arrhythmia, classically torsade de pointes. This predisposition to malignant arrhythmia is from a cardiac ion channelopathy that results in delayed repolarization of the cardiomyocyte action potential. The QT interval on the surface electrocardiogram is a summation of the individual cellular ventricular action potential durations, and hence is a surrogate marker of the abnormal cellular membrane repolarization. Severely affected phenotypes administered current standard of care therapies may not be fully protected from the occurrence of cardiac arrhythmias. There are 17 different subtypes of LQTS associated with monogenic mutations of 15 autosomal dominant genes. It is now possible to model the various LQTS phenotypes through the generation of patient-specific induced pluripotent stem cell-derived cardiomyocytes. RNA interference can silence or suppress the expression of mutant genes. Thus, RNA interference can be a potential therapeutic intervention that may be employed in LQTS to knock out mutant mRNAs which code for the defective proteins. CRISPR/Cas9 is a genome editing technology that offers great potential in elucidating gene function and a potential therapeutic strategy for monogenic disease. Further studies are required to determine whether CRISPR/Cas9 can be employed as an efficacious and safe rescue of the LQTS phenotype. Current progress has raised opportunities to generate in vitro human cardiomyocyte models for drug screening and to explore gene therapy through genome editing.

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Section: Genetics Of Lqtsmentioning

confidence: 99%

Section: Genetics Of Lqtsmentioning

confidence: 99%

Long QT Syndrome: Genetics and Future Perspective

et al. 2019

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“…It was shown that PKA-mediated phosphorylation of KCNQ1 at serine 27 is critical for I Ks . Yotiao (AKAP9) effectively scaffolds PKA and protein phosphatase-1 (PP-1) to KCNQ1, maintaining its phosphorylation levels during upstream receptor activation [ 41 ]. The S1570L mutation was found in the KCNQ1-binding domain of yotiao, representing 2% of the clinically-robust LQTS-exhibiting patients.…”

Section: Polymorphisms/mutations In Akaps and Cvdsmentioning

confidence: 99%

Polymorphisms/Mutations in A-Kinase Anchoring Proteins (AKAPs): Role in the Cardiovascular System

Suryavanshi

Jadhav

McConnell

2018

JCDD

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A-kinase anchoring proteins (AKAPs) belong to a family of scaffolding proteins that bind to protein kinase A (PKA) by definition and a variety of crucial proteins, including kinases, phosphatases, and phosphodiesterases. By scaffolding these proteins together, AKAPs build a “signalosome” at specific subcellular locations and compartmentalize PKA signaling. Thus, AKAPs are important for signal transduction after upstream activation of receptors ensuring accuracy and precision of intracellular PKA-dependent signaling pathways. Since their discovery in the 1980s, AKAPs have been studied extensively in the heart and have been proven essential in mediating cyclic adenosine monophosphate (cAMP)-PKA signaling. Although expression of AKAPs in the heart is very low, cardiac-specific knock-outs of several AKAPs have a noteworthy cardiac phenotype. Moreover, single nucleotide polymorphisms and genetic mutations in crucial cardiac proteins play a substantial role in the pathophysiology of cardiovascular diseases (CVDs). Despite the significant role of AKAPs in the cardiovascular system, a limited amount of research has focused on the role of genetic polymorphisms and/or mutations in AKAPs in increasing the risk of CVDs. This review attempts to overview the available literature on the polymorphisms/mutations in AKAPs and their effects on human health with a special focus on CVDs.

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“…Delayed rectified potassium channels are responsible for ventricular repolarization and stabilization of membrane potential. With disruption of the normal function of these channels and multiple potassium currents, electrical instability may result in malignant tachyarrhythmias [7].…”

Section: Discussionmentioning

confidence: 99%

QT Independent Ventricular Tachycardia Induced by Arsenic Trioxide

Zeitjian

Moazez

Arslan

et al. 2019

Case Reports in Cardiology

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Arsenic trioxide (ATO) is commonly known to cause QT prolongation with resultant ventricular tachycardia (VT). VT, independent of QT prolongation, can be a complication of ATO. We present a 46-year-old female who received ATO and during her hospital course had intermittent nonsustained VT. All usual causes of VT were considered including reduced EF < 35%, ischemia, electrolyte abnormalities, medications, and genetic polymorphisms; however, no specific cause was found. After stopping therapy, the episodes of nonsustained VT ceased indicating that there is an association between ATO and VT.

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Cardiac Delayed Rectifier Potassium Channels in Health and Disease

Cited by 54 publications

References 182 publications

Long QT Syndrome: Genetics and Future Perspective

Long QT Syndrome: Genetics and Future Perspective

Polymorphisms/Mutations in A-Kinase Anchoring Proteins (AKAPs): Role in the Cardiovascular System

QT Independent Ventricular Tachycardia Induced by Arsenic Trioxide

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