ArticleBiophysical journal2012
K⁺ conduction and Mg²⁺ blockade in a shaker Kv-channel single point mutant with an unusually high conductance.
Article in Biophysical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Ion Channel Reaction Networks: Dielectric Screening and the Importance of Off-Pathway Flux.Journal of chemical theory and computation · 2025Article
- Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.Journal of chemical theory and computation · 2025Article
- Nernst equilibrium, rectification, and saturation: Insights into ion channel behavior.Biophysical journal · 2024Article
- Nernst Equilibrium, Rectification, and Saturation: Insights into Ion Channel Behavior.bioRxiv : the preprint server for biology · 2024Article
- Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.bioRxiv : the preprint server for biology · 2024Article
- Sweetening K-channels: what sugar taught us about permeation and gating.Frontiers in molecular biosciences · 2023Review
- The nonconducting W434F mutant adopts upon membrane depolarization an inactivated-like state that differs from wild-type Shaker-IR potassium channels.Science advances · 2022Article
- Pore size matters for potassium channel conductance.The Journal of general physiology · 2016Review
- Pore dimensions and the role of occupancy in unitary conductance of Shaker K channels.The Journal of general physiology · 2015Article
- What keeps Kv channels small? The molecular physiology of modesty.The Journal of general physiology · 2015Article
- Hydrophobic interaction between contiguous residues in the S6 transmembrane segment acts as a stimuli integration node in the BK channel.The Journal of general physiology · 2015Article
- Initial steps of inactivation at the K+ channel selectivity filter.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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8 authors.
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Abstract
Potassium channels exhibit a large diversity of single-channel conductances. Shaker is a low-conductance K-channel in which Pro475→Asp, a single-point mutation near the internal pore entrance, promotes 6- to 8-fold higher unitary current. To assess the mechanism for this higher conductance, we measured Shaker-P475D single-channel current in a wide range of symmetrical K(+) concentrations and voltages. Below 300 mM K(+), the current-to-voltage relations (i-V) showed inward rectification that disappeared at 1000 mM K(+). Single-channel conductance reached a maximum of ∼190 pS at saturating [K(+)], a value 4- to 5-fold larger than that estimated for the native channel. Intracellular Mg(2+) blocked this variant with ∼100-fold higher affinity. Near zero voltage, blockade was competitively antagonized by K(+); however, at voltages >100 mV, it was enhanced by K(+). This result is consistent with a lock-in effect in a single-file diffusion regime of Mg(2+) and K(+) along the pore. Molecular-dynamics simulations revealed higher K(+) density in the pore, especially near the Asp-475 side chains, as in the high-conductance MthK bacterial channel. The molecular dynamics also showed that K(+) ions bound distally can coexist with other K(+) or Mg(2+) in the cavity, supporting a lock-in mechanism. The maximal K(+) transport rate and higher occupancy could be due to a decrease in the electrostatic energy profile for K(+) throughout the pore, reducing the energy wells and barriers differentially by ∼0.7 and ∼2 kT, respectively.
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