Physical and Functional Interaction Sites in Cytoplasmic Domains of KCNQ1 and KCNE1 Channel Subunits.

Physical and Functional Interaction Sites in Cytoplasmic Domains of KCNQ1 and KCNE1 Channel Subunits. Am J Physiol Heart Circ Physiol. 2019 Dec 13;: Authors: Chen J, Liu Z, Creagh JP, Zheng R, McDonald TV Abstract The cardiac potassium IKs current is carried by a channel complex formed from a-subunits encoded by KCNQ1 and b-subunits encoded by KCNE1. Deleterious mutations in either gene are associated with hereditary long QT syndrome. Interactions between the transmembrane domains of the a- and b-subunits determine the activation kinetics of IKs. A physical and functional interaction between C-termini of the proteins has also been identified that impacts deactivation rate and voltage-dependence of activation. We sought to explore the specific physical interactions between the C-termini of the subunits that confer such control. Hydrogen/deuterium exchange coupled to mass spectrometry narrowed down the region of interaction to KCNQ1 residues 352-374 and KCNE1 residues 70-81, and provided evidence of secondary structure within these segments. Key mutations of residues in these regions tended to shift voltage dependence of activation toward more depolarizing voltages. Double mutant cycle analysis then revealed energetic coupling between KCNQ1-I368 and KCNE1-D76 during channel activation. Our results suggest that the proximal C-terminal regions of KCNQ1 and KCNE1 participate in a physical and functional interaction during channel opening that is sensitive to ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research

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CONCLUSION:  The results indicate that the methods applied would be efficient for the identification of these genetic cardiac diseases. PMID: 32079026 [PubMed - as supplied by publisher]
Source: Methods of Information in Medicine - Category: Information Technology Authors: Tags: Methods Inf Med Source Type: research
The human ether-á-go-go–related gene (hERG1) channel conducts small outward K+ currents that are critical for cardiomyocyte membrane repolarization. The gain-of-function mutation N629D at the outer mouth of the selectivity filter (SF) disrupts inactivation and K+-selective transport in hERG1, leading to arrhythmogenic phenotypes associated with long-QT syndrome. Here, we combined computational...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
KCNE1 loss-of-function variants cause type 5 long QT syndrome (LQT5). However, most alleged LQT5-causative KCNE1 variants were identified before the true rate of background genetic variation was appreciated fully.
Source: Heart Rhythm - Category: Cardiology Authors: Source Type: research
Publication date: Available online 6 February 2020Source: Stem Cell ResearchAuthor(s): Hong-Mei Zhou, Xiao-Qian Zhou, Ji-Zhen Lu, Wen-Wen Jia, Jiu-Hong KangAbstractLong QT syndrome type 8 is an uncommon inherited condition .An induced pluripotent stem cell (iPSC) line was generated from Peripheral blood mononuclear cells (PBMCs) of a 10-year-old patient with heterozygous mutation of p.R858H(c.2573G>A )in the CACNA1C gene. This iPSC model offers a very valuable resource to study the disease pathophysiology and to develop therapeutics for treatment of Long QT syndrome type 8 patients.
Source: Stem Cell Research - Category: Stem Cells Source Type: research
NIH-funded ClinGen panel also validates three genes believed to be associated with Long QT syndrome.
Source: National Institutes of Health (NIH) News Releases - Category: American Health Source Type: news
PMID: 31983240 [PubMed - as supplied by publisher]
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
Acquired long QT syndrome is a well-described pathology in the pediatric population. Previous publications demonstrated that patients undergoing hematopoietic stem cell transplantation (HSCT) can develop cardiac complications, and several of these patients develop drug-induced long QT syndrome in the post-transplant period. Previous publications suggest that HSCT patients present significant QT prolongation in the early post-transplantation period.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 184 Source Type: research
lini C, Shimamoto K, Tadros R, Cadrin-Tourigny J, Duff HJ, Simpson CS, Roston TM, Wijeyeratne YD, El Hajjaji I, Yousif MD, Gula LJ, Leong-Sit P, Chavali N, Landstrom AP, Marcus GM, Dittmann S, Wilde AAM, Behr ER, Tfelt-Hansen J, Scheinman MM, Perez MV, Kaski JP, Gow RM, Drago F, Aziz PF, Abrams DJ, Gollob MH, Skinner JR, Shimizu W, Kaufman ES, Roden DM, Zareba W, Schwartz PJ, Schulze-Bahr E, Etheridge SP, Priori SG, Ackerman MJ Abstract Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic featu...
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
We examined frequency, clinical characteristics and AF‐related management and outcomes amongst this patient population.MethodsWe retrospectively studied consecutive probands with inherited cardiomyopathy (n=962) and inherited arrhythmia syndromes (n=195) evaluated between 2002 ‐2018.ResultsAF was observed in 5 ‐31% of patients, with the highest frequency in HCM. Age of AF onset was 45.8 ± 21.9 years in the inherited arrhythmia syndromes compared to 53.3 ± 15.3 years in the inherited cardiomyopathies, with 4 CPVT patients developing AF at median age of 20 years. Overall, 11% of patients with AF had a t r...
Source: Journal of Cardiovascular Electrophysiology - Category: Cardiology Authors: Tags: ORIGINAL ARTICLE Source Type: research
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Source: Frontiers in Physiology - Category: Physiology Source Type: research
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