ArticleThe Journal of general physiology2004
Gating charges in the activation and inactivation processes of the HERG channel.
Article in The Journal of general physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 108 citations in OpenAlex.
- Allosteric Mechanisms Underlying Long QT Syndrome Type 2 (LQT2)-Associated Mutations in hERG Channels.bioRxiv : the preprint server for biology · 2026Article
- Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026Review
- Ion Channel-Targeting Toxins: Structural Mechanisms of Activation, Inhibition, and Therapeutic Potential.Toxins · 2025Review
- Voltage sensor conformations induced by LQTS-associated mutations in hERG potassium channels.Nature communications · 2025Article
- An Allosteric Model for Electromechanical Coupling in Cardiac CNBD Channels.bioRxiv : the preprint server for biology · 2025Article
- Voltage sensors.Molecular pharmacology · 2025Review
- Potassium dependent structural changes in the selectivity filter of HERG potassium channels.Nature communications · 2024Article
- Evaluating sequential and allosteric activation models in IKs channels with mutated voltage sensors.The Journal of general physiology · 2024Article
- An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG.BMC biology · 2024Article
- Integrins regulate hERG1 dynamics by girdin-dependent Gαi3: signaling and modeling in cancer cells.Life science alliance · 2024Article
- Integrated Approach Including Docking, MD Simulations, and Network Analysis Highlights the Action Mechanism of the Cardiac hERG Activator RPR260243.Journal of chemical information and modeling · 2023Article
- Noncanonical electromechanical coupling paths in cardiac hERG potassium channel.Nature communications · 2023Article
- Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues.Science advances · 2022Article
- The voltage-sensing domain of a hERG1 mutant is a cation-selective channel.Biophysical journal · 2022Article
- Voltage-sensor movements in the Eag Kv channel under an applied electric field.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Precise in vivo functional analysis of DNA variants with base editing using ACEofBASEs target prediction.eLife · 2022Article
- Molecular dynamics simulations suggest possible activation and deactivation pathways in the hERG channel.Communications biology · 2022Article
- Lipid regulation of hERG1 channel function.Nature communications · 2021Article
- Refinement of a cryo-EM structure of hERG: Bridging structure and function.Biophysical journal · 2021Article
- Mechanism of hERG inhibition by gating-modifier toxin, APETx1, deduced by functional characterization.BMC molecular and cell biology · 2021Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The hERG channel has a relatively slow activation process but an extremely fast and voltage-sensitive inactivation process. Direct measurement of hERG's gating current (Piper, D.R., A. Varghese, M.C. Sanguinetti, and M. Tristani-Firouzi. 2003. PNAS. 100:10534-10539) reveals two kinetic components of gating charge transfer that may originate from two channel domains. This study is designed to address three questions: (1) which of the six positive charges in hERG's major voltage sensor, S4, are responsible for gating charge transfer during activation, (2) whether a negative charge in the cytoplasmic half of S2 (D466) also contributes to gating charge transfer, and (3) whether S4 serves as the sole voltage sensor for hERG inactivation. We individually mutate S4's positive charges and D466 to cysteine, and examine (a) effects of mutations on the number of equivalent gating charges transferred during activation (z(a)) and inactivation (z(i)), and (b) sidedness and state dependence of accessibility of introduced cysteine side chains to a membrane-impermeable thiol-modifying reagent (MTSET). Neutralizing the outer three positive charges in S4 and D466 in S2 reduces z(a), and cysteine side chains introduced into these positions experience state-dependent changes in MTSET accessibility. On the other hand, neutralizing the inner three positive charges in S4 does not affect z(a). None of the charge mutations affect z(i). We propose that the scheme of gating charge transfer during hERG's activation process is similar to that described for the Shaker channel, although hERG has less gating charge in its S4 than in Shaker. Furthermore, channel domain other than S4 contributes to gating charge involved in hERG's inactivation process.
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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.