ArticleThe Journal of general physiology2013
Functional interactions of voltage sensor charges with an S2 hydrophobic plug in hERG channels.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Bdelloid rotifers harbor a voltage-gated proton channel with distinct mechanistic features.Nature communications · 2026Article
- Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026Review
- An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG.BMC biology · 2024Article
- The voltage-sensing domain of a hERG1 mutant is a cation-selective channel.Biophysical journal · 2022Article
- The role of Phe150 in human voltage-gated proton channel.iScience · 2022Article
- Electrophysiological characterization of the hERG R56Q LQTS variant and targeted rescue by the activator RPR260243.The Journal of general physiology · 2021Article
- Refinement of a cryo-EM structure of hERG: Bridging structure and function.Biophysical journal · 2021Article
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- Investigating the utility of adult zebrafish ex vivo whole hearts to pharmacologically screen hERG channel activator compounds.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
- Extracellular protons accelerate hERG channel deactivation by destabilizing voltage sensor relaxation.The Journal of general physiology · 2019Article
- An Update on the Structure of hERG.Frontiers in pharmacology · 2019Review
- Calcium channel gating.Pflugers Archiv : European journal of physiology · 2018Review
- The Fast Component of hERG Gating Charge: An Interaction between D411 in the S1 and S4 Residues.Biophysical journal · 2017Article
- Stabilization of the Activated hERG Channel Voltage Sensor by Depolarization Involves the S4-S5 Linker.Biophysical journal · 2017Article
- Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels.Scientific reports · 2016Article
- Molecular Interactions in the Voltage Sensor Controlling Gating Properties of CaV Calcium Channels.Structure (London, England : 1993) · 2016Article
- Intra- and Intersubunit Dynamic Binding in Kv4.2 Channel Closed-State Inactivation.Biophysical journal · 2016Article
- NS1643 interacts around L529 of hERG to alter voltage sensor movement on the path to activation.Biophysical journal · 2015Article
- Voltage sensor gating charge transfer in a hERG potassium channel model.Biophysical journal · 2014Article
- A self-consistent approach for determining pairwise interactions that underlie channel activation.The Journal of general physiology · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human ether-à-go-go-related gene (hERG, Kv11.1) potassium channels have unusually slow activation and deactivation kinetics. It has been suggested that, in fast-activating Shaker channels, a highly conserved Phe residue (F290) in the S2 segment forms a putative gating charge transfer center that interacts with S4 gating charges, i.e., R362 (R1) and K374 (K5), and catalyzes their movement across the focused electric field. F290 is conserved in hERG (F463), but the relevant residues in the hERG S4 are reversed, i.e., K525 (K1) and R537 (R5), and there is an extra positive charge adjacent to R537 (i.e., K538). We have examined whether hERG channels possess a transfer center similar to that described in Shaker and if these S4 charge differences contribute to slow gating in hERG channels. Of five hERG F463 hydrophobic substitutions tested, F463W and F463Y shifted the conductance-voltage (G-V) relationship to more depolarized potentials and dramatically slowed channel activation. With the S4 residue reversals (i.e., K525, R537) taken into account, the closed state stabilization by F463W is consistent with a role for F463 that is similar to that described for F290 in Shaker. As predicted from results with Shaker, the hERG K525R mutation destabilized the closed state. However, hERG R537K did not stabilize the open state as predicted. Instead, we found the neighboring K538 residue to be critical for open state stabilization, as K538R dramatically slowed and right-shifted the voltage dependence of activation. Finally, double mutant cycle analysis on the G-V curves of F463W/K525R and F463W/K538R double mutations suggests that F463 forms functional interactions with K525 and K538 in the S4 segment. Collectively, these data suggest a role for F463 in mediating closed-open equilibria, similar to that proposed for F290 in Shaker channels.
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