ArticleBiophysical journal2006
Modulation of HERG gating by a charge cluster in the N-terminal proximal domain.
Article in Biophysical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- The ERG1 KFrontiers in molecular neuroscience · 2022Review
- Electrophysiological characterization of the modified hERGPhysiological reports · 2020Article
- Relative positioning of Kv11.1 (hERG) KScientific reports · 2018Article
- Two mutations at different positions in the CNBH domain of the hERG channel accelerate deactivation and impair the interaction with the EAG domain.The Journal of physiology · 2018Article
- Determinants of Isoform-Specific Gating Kinetics of hERG1 Channel: Combined Experimental and Simulation Study.Frontiers in physiology · 2018Article
- An Interdomain KCNH2 Mutation Produces an Intermediate Long QT Syndrome.Human mutation · 2015Article
- Article
- The eag domain regulates hERG channel inactivation gating via a direct interaction.The Journal of general physiology · 2013Article
- Voltage-dependent gating of HERG potassium channels.Frontiers in pharmacology · 2012Article
- Cytoplasmic domains and voltage-dependent potassium channel gating.Frontiers in pharmacology · 2012Article
- The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating.PloS one · 2012Article
- Demonstration of physical proximity between the N terminus and the S4-S5 linker of the human ether-a-go-go-related gene (hERG) potassium channel.The Journal of biological chemistry · 2011Article
- Molecular determinants of interactions between the N-terminal domain and the transmembrane core that modulate hERG K+ channel gating.PloS one · 2011Article
- Role of ERG1 isoforms in modulation of ERG1 channel trafficking and function.Pflugers Archiv : European journal of physiology · 2010Review
- Participation of HERG channel cytoplasmic structures on regulation by the G protein-coupled TRH receptor.Pflugers Archiv : European journal of physiology · 2009Article
- Thermodynamic and kinetic properties of amino-terminal and S4-S5 loop HERG channel mutants under steady-state conditions.Biophysical journal · 2008Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human ether-a-go-go-related gene (HERG) potassium channels contribute to the repolarization of the cardiac action potential and display unique gating properties with slow activation and fast inactivation kinetics. Deletions in the N-terminal 'proximal' domain (residues 135-366) have been shown to induce hyperpolarizing shifts in the voltage dependence of activation, suggesting that it modulates activation. However, we did not observe a hyperpolarizing shift with a subtotal deletion designed to preserve the local charge distribution, and other deletions narrowed the region to the KIKER containing sequence 362-372. Replacing the positively charged residues of this sequence by negative ones (EIEEE) resulted in a -45 mV shift of the voltage dependence of activation. The shifts were intermediate for individual charge reversals, whereas E365R resulted in a positive shift. Furthermore, the shifts in the voltage dependence were strongly correlated with the net charge of the KIKER region. The apparent speeding of the activation was attributable to the shifted voltage dependence of activation. Additionally, the introduction of negative charges accelerated the intermediate voltage-independent forward rate constant. We propose that the modulatory effects of the proximal domain on HERG gating are largely electrostatic, localized to the charged KIKER sequence.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.