ArticleThe Journal of general physiology2013
Free-energy relationships in ion channels activated by voltage and ligand.
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.
- Ligand Binding Dynamics of Ion Channels and GPCRs Using Single-Molecule Fluorescence.Annual review of biophysics · 2026Review
- Markov models and long-term memory in ion channels: A contradiction in terms?Biophysical journal · 2025Article
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- A critical residue in the αeLife · 2021Article
- Photons detected in the active nerve by photographic technique.Scientific reports · 2021Article
- Article
- The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as Shown by Quantum Calculations.Sensors (Basel, Switzerland) · 2018Article
- Gating currents.The Journal of general physiology · 2018Review
- Activation gating in HCN2 channels.PLoS computational biology · 2018Article
- Node of Ranvier as an Array of Bio-Nanoantennas for Infrared Communication in Nerve Tissue.Scientific reports · 2018Article
- Structure and Energetics of Allosteric Regulation of HCN2 Ion Channels by Cyclic Nucleotides.The Journal of biological chemistry · 2016Article
- KCNE3 acts by promoting voltage sensor activation in KCNQ1.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- A self-consistent approach for determining pairwise interactions that underlie channel activation.The Journal of general physiology · 2014Article
- Interfacial gating triad is crucial for electromechanical transduction in voltage-activated potassium channels.The Journal of general physiology · 2014Article
- Article
- A nonequilibrium binary elements-based kinetic model for benzodiazepine regulation of GABAA receptors.The Journal of general physiology · 2014Article
- Modeling ion channels: past, present, and future.The Journal of general physiology · 2014Review
- Mutation of I696 and W697 in the TRP box of vanilloid receptor subtype I modulates allosteric channel activation.The Journal of general physiology · 2014Article
- Coarse-grained simulations of the gating current in the voltage-activated Kv1.2 channel.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Hydrophobic plug functions as a gate in voltage-gated proton channels.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
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Abstract
Many ion channels are modulated by multiple stimuli, which allow them to integrate a variety of cellular signals and precisely respond to physiological needs. Understanding how these different signaling pathways interact has been a challenge in part because of the complexity of underlying models. In this study, we analyzed the energetic relationships in polymodal ion channels using linkage principles. We first show that in proteins dually modulated by voltage and ligand, the net free-energy change can be obtained by measuring the charge-voltage (Q-V) relationship in zero ligand condition and the ligand binding curve at highly depolarizing membrane voltages. Next, we show that the voltage-dependent changes in ligand occupancy of the protein can be directly obtained by measuring the Q-V curves at multiple ligand concentrations. When a single reference ligand binding curve is available, this relationship allows us to reconstruct ligand binding curves at different voltages. More significantly, we establish that the shift of the Q-V curve between zero and saturating ligand concentration is a direct estimate of the interaction energy between the ligand- and voltage-dependent pathway. These free-energy relationships were tested by numerical simulations of a detailed gating model of the BK channel. Furthermore, as a proof of principle, we estimate the interaction energy between the ligand binding and voltage-dependent pathways for HCN2 channels whose ligand binding curves at various voltages are available. These emerging principles will be useful for high-throughput mutagenesis studies aimed at identifying interaction pathways between various regulatory domains in a polymodal ion channel.
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