hERG1a and hERG1b potassium channel subunits directly interact and preferentially form heteromeric channels
TLDR
HERG1b preferentially forms heteromeric ion channels with hERG1a at the plasma membrane, and multiple lines of evidence indicated a physical interaction between hERG 1a and hERG2b, consistent with them forming heteromerics channels.About:
This article is published in Journal of Biological Chemistry.The article was published on 2017-12-29 and is currently open access. It has received 19 citations till now. The article focuses on the topics: Ion channel & Potassium channel.read more
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Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.
TL;DR: In an effort to encapsulate the breadth over which fluorescent biosensors have expanded, this work endeavored to assemble a comprehensive list of published engineered bios Sensors, and discusses many of the molecular designs utilized in their development.
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Drug-induced Proarrhythmia and Torsade de Pointes: A Primer for Students and Practitioners of Medicine and Pharmacy
J. Rick Turner,Ignacio Rodriguez,Emily H Mantovani,Gary Gintant,Peter R. Kowey,Ralph J Klotzbaugh,Krishna Prasad,Philip T. Sager,Norman Stockbridge,Colette Strnadova +9 more
TL;DR: This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety‐related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhalic liability.
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A microtranslatome coordinately regulates sodium and potassium currents in the human heart.
Catherine A. Eichel,Erick B. Ríos-Pérez,Fang Liu,Margaret B. Jameson,David K. Jones,Jennifer J. Knickelbine,Gail A. Robertson +6 more
TL;DR: It is found that roughly half the hERG translational complexes contain SCN5A transcripts, and association and coordinate regulation of transcripts in discrete ‘microtranslatomes’ represents a new paradigm controlling electrical activity in heart and other excitable tissues.
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Fentanyl-Induced Block of hERG Channels Is Exacerbated by Hypoxia, Hypokalemia, Alkalosis, and the Presence of hERG1b.
TL;DR: It is demonstrated that heterologously expressed human ether a-go-go–related gene (hERG) 1a/1b channels, which more closely resemble rapidly activating delayed rectifier potassium current in the human heart, are blocked by fentanyl with a 3-fold greater potency than the previously studied hERG1a expressed alone.
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Long QT Syndrome KCNH2 Variant Induces hERG1a/1b Subunit Imbalance in Patient-Specific Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Li Feng,Jianhua Zhang,ChangHwan Lee,Gina Kim,Fang Liu,Andrew J. Petersen,Evi Lim,Corey L. Anderson,Kate M. Orland,Gail A. Robertson,Lee L. Eckhardt,Craig T. January,Timothy J. Kamp +12 more
TL;DR: In this paper, patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were derived from a LQT syndrome type 2 (LQT2) patient carrying the PAS domain variant hERG1-H70R.
References
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Electrophysiological Characterization of an Alternatively Processed ERG K+ Channel in Mouse and Human Hearts
TL;DR: ERG B, an alternatively processed isoform of the ERG gene, expressed selectively in heart and with electrophysiological characteristics similar to those of native cardiac IKr is identified.
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Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells.
Garth A.M. Smith,Hing-Wo Tsui,Evan W. Newell,Xinpo Jiang,Xiaoping Zhu,Florence W. L. Tsui,Lyanne C. Schlichter +6 more
TL;DR: The selective HERG channel blocker, E-4031, reduced proliferation of CEM, U937, and K562 cells, and this appears to be the first direct evidence of a functional role for the HERG current in cancer cells.
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Cell Cycle-dependent Expression of HERG1 and HERG1B Isoforms in Tumor Cells
Olivia Crociani,Leonardo Guasti,Manuela Balzi,Andrea Becchetti,Enzo Wanke,Massimo Olivotto,Randy S. Wymore,Annarosa Arcangeli +7 more
TL;DR: It is demonstrated that in tumor cells the value of V m is clamped to rather depolarized values by K+ channels belonging to the HERG family, suggesting that modulated expression of different K+ channel is the molecular basis of a novel mechanism regulating neoplastic cell proliferation.
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Cardiac IKr channels minimally comprise hERG 1a and 1b subunits.
TL;DR: These data indicate native ventricular IKr channels are heteromers containing two α subunit types, ERG1a and -1b, and suggest phenotypic analyses of existing type 2 long QT syndrome mutations should be carried out in systems expressing both subunits.
Journal ArticleDOI
Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome
Corey L. Anderson,Catherine E. Kuzmicki,Ryan R. Childs,Caleb J. Hintz,Brian P. Delisle,Craig T. January +5 more
TL;DR: A comprehensive analysis of 167 LQT2-linked missense mutations in four Kv11.1 structural domains found that deficient protein trafficking is the dominant mechanism for all domains except for the distal C-terminus and pharmacological correction is dramatically improved for pore mutants when co-expressed with wild type subunits to form heteromeric channels.