ArticleProceedings of the National Academy of Sciences of the United States of America2013
Single-channel basis for the slow activation of the repolarizing cardiac potassium current, I(Ks).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Electrophysiological characterization of the state-dependent inhibition of Kv7.1 and IMolecular pharmacology · 2025Article
- A physiologically-relevant intermediate state structure of a voltage-gated potassium channel.Nature communications · 2025Article
- Ion permeation through a narrow cavity constriction in KCNQ1 channels: Mechanism and implications for pathogenic variants.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Evaluating sequential and allosteric activation models in IKs channels with mutated voltage sensors.The Journal of general physiology · 2024Article
- Mechanism of external K+ sensitivity of KCNQ1 channels.The Journal of general physiology · 2023Article
- Emerging methods to model cardiac ion channel and myocyte electrophysiology.Biophysics reviews · 2023Review
- Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277.Nature communications · 2022Article
- ML277 regulates KCNQ1 single-channel amplitudes and kinetics, modified by voltage sensor state.The Journal of general physiology · 2021Article
- A549 in-silico 1.0: A first computational model to simulate cell cycle dependent ion current modulation in the human lung adenocarcinoma.PLoS computational biology · 2021Article
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Insights into Cardiac IKs (KCNQ1/KCNE1) Channels Regulation.International journal of molecular sciences · 2020Review
- Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.Frontiers in physiology · 2020Review
- Article
- The KThe Journal of physiology · 2019Article
- Article
- The IBiophysical journal · 2018Article
- Effects of β-subunit on gating of a potassium ion channel: Molecular simulations of cardiac IKs activation.Journal of molecular and cellular cardiology · 2018Article
- Four drug-sensitive subunits are required for maximal effect of a voltage sensor-targeted KCNQ opener.The Journal of general physiology · 2018Article
- Modeling the Hidden Pathways of IKs Channel Activation.Biophysical journal · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Coassembly of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with potassium voltage-gated channel, Isk-related family, member 1 (KCNE1) the delayed rectifier potassium channel I(Ks). Its slow activation is critically important for membrane repolarization and for abbreviating the cardiac action potential, especially during sympathetic activation and at high heart rates. Mutations in either gene can cause long QT syndrome, which can lead to fatal arrhythmias. To understand better the elementary behavior of this slowly activating channel complex, we quantitatively analyzed direct measurements of single-channel I(Ks). Single-channel recordings from transiently transfected mouse ltk(-) cells confirm a channel that has long latency periods to opening (1.67 ± 0.073 s at +60 mV) but that flickers rapidly between multiple open and closed states in non-deactivating bursts at positive membrane potentials. Channel activity is cyclic with periods of high activity followed by quiescence, leading to an overall open probability of only ∼0.15 after 4 s under our recording conditions. The mean single-channel conductance was determined to be 3.2 pS, but unlike any other known wild-type human potassium channel, long-lived subconductance levels coupled to activation are a key feature of both the activation and deactivation time courses of the conducting channel complex. Up to five conducting levels ranging from 0.13 to 0.66 pA could be identified in single-channel recordings at 60 mV. Fast closings and overt subconductance behavior of the wild-type I(Ks) channel required modification of existing Markov models to include these features of channel behavior.
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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.