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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Physiological Properties of hERG 1a/1b Heteromeric Currents and a hERG 1b-Specific Mutation Associated With Long-QT Syndrome
Harinath Sale,Jinling Wang,Thomas O'Hara,David J. Tester,Pallavi Phartiyal,Jia-Qiang He,Yoram Rudy,Michael J. Ackerman,Gail A. Robertson +8 more
TL;DR: Heteromeric hERG 1a/1b channels were inhibited by E-4031 with a slower time course and a corresponding 4-fold shift in the IC50, which represents a potential mechanism underlying inherited or acquired LQTS.
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hERG potassium channel gating is mediated by N- and C-terminal region interactions.
TL;DR: The data suggest that the mechanism for regulation of slow deactivation in hERG channels is an interaction between the N-terminal PAS domain and the C-terminals of the CNBD.
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A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channels.
TL;DR: This study demonstrates that direct, noncovalent interactions between the eag domain and the channel core were sufficient to regulate deactivation gating, that an LQTS mutation perturbed physical interactions between an N-terminal domain and a channel core, and that small molecules such as the Eag domain represent a novel method for restoring function to channels with disease-causing mutations.
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Structure and dynamics of Escherichia coli chemosensory receptors. Engineered sulfhydryl studies
TL;DR: In this paper, the conformation and dynamics of two receptors in the E. coli chemotaxis pathway have been investigated, and the results suggest that thermal backbone motions may have larger amplitudes than previously thought.
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hERG 1b is critical for human cardiac repolarization
David K. Jones,Fang Liu,Ravi Vaidyanathan,Lee L. Eckhardt,Matthew C. Trudeau,Gail A. Robertson +5 more
TL;DR: It is found that specific knockdown of the 1b subunit using shRNA caused reductions in 1b mRNA, 1b protein levels, and IKr magnitude by roughly one-half, establishing that hERG 1b is critical for normal repolarization and that loss of 1a is proarrhythmic in human cardiac cells.