ArticleThe Journal of general physiology2013
External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- New insights into the physiological, pathological and pharmacological roles of voltage‑gated potassium channel Kv10.1 in cancer (Review).International journal of oncology · 2026Review
- Apoplastic metabolomics reveals sugars as mesophyll messengers regulating guard cell ion transport under red light.Nature plants · 2025Article
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- A broad survey of choanoflagellates revises the evolutionary history of the Shaker family of voltage-gated KProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Architecture and rearrangements of a sperm-specific NaResearch square · 2023Article
- Kv12-encoded K+ channels drive the day-night switch in the repetitive firing rates of SCN neurons.The Journal of general physiology · 2023Article
- hERG1 channel subunit composition mediates proton inhibition of rapid delayed rectifier potassium current (IThe Journal of biological chemistry · 2023Article
- The Kv10.1 Channel: A Promising Target in Cancer.International journal of molecular sciences · 2022Review
- External Cd2+ and protons activate the hyperpolarization-gated K+ channel KAT1 at the voltage sensor.The Journal of general physiology · 2021Article
- Plant Proton Pumps and Cytosolic pH-Homeostasis.Frontiers in plant science · 2021Review
- pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.Cancers · 2020Review
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- Identification of a proton sensor that regulates conductance and open time of single hERG channels.Scientific reports · 2019Article
- Histidine at position 462 determines the low quinine sensitivity of ether-à-go-go channel superfamily member KBritish journal of pharmacology · 2019Article
- Extracellular protons accelerate hERG channel deactivation by destabilizing voltage sensor relaxation.The Journal of general physiology · 2019Article
- Ether-à-go-go KThe Journal of physiology · 2018Review
- KChannels (Austin, Tex.) · 2018Article
- Inverse Modulation of Neuronal KFrontiers in molecular neuroscience · 2018Article
- EAG channels expressed in microvillar photoreceptors are unsuited to diurnal vision.The Journal of physiology · 2017Article
- The involvement of Eag1 potassium channels and miR-34a in rotenone-induced death of dopaminergic SH-SY5Y cells.Molecular medicine reports · 2017Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The Ether-a-go-go (EAG) superfamily of voltage-gated K(+) channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K(+) currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K(+) channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance-voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn(2+). Low pH similarly reduces Mg(2+) sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca(2+). Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K(+) currents observed in vivo.
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