ArticleProceedings of the National Academy of Sciences of the United States of America2014
Chemoselective tarantula toxins report voltage activation of wild-type ion channels in live cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Precise and Stable Labeling of Quantum Dots with Engineered Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers.eLife · 2025Article
- The Electrically Silent Kv5.1 Subunit Forms Heteromeric Kv2 Channels in Cortical Neurons and Confers Distinct Functional Properties.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Shining a Light on Venom-Peptide Receptors: Venom Peptides as Targeted Agents for In Vivo Molecular Imaging.Toxins · 2024Review
- Neurotoxin-Derived Optical Probes for Biological and Medical Imaging.Molecular imaging and biology · 2023Review
- Mechanism of use-dependent Kv2 channel inhibition by RY785.The Journal of general physiology · 2022Article
- The AMIGO1 adhesion protein activates Kv2.1 voltage sensors.Biophysical journal · 2022Article
- EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues.The Journal of general physiology · 2021Article
- Peptide Toxins Targeting KV Channels.Handbook of experimental pharmacology · 2021Review
- Distinguishing Potassium Channel Resting State Conformations in Live Cells with Environment-Sensitive Fluorescence.ACS chemical neuroscience · 2020Article
- An Activity-Based Methionine Bioconjugation Approach To Developing Proximity-Activated Imaging Reporters.ACS central science · 2020Article
- Neuronal ER-plasma membrane junctions organized by Kv2-VAP pairing recruit Nir proteins and affect phosphoinositide homeostasis.The Journal of biological chemistry · 2019Article
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- Unlocking the gating mechanism of Kv2.1 using guangxitoxin.The Journal of general physiology · 2019Article
- The tarantula toxin GxTx detains KThe Journal of general physiology · 2019Article
- Remodeling neuronal ER-PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels.Molecular biology of the cell · 2018Article
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- Article
- Regulation of voltage-gated potassium channels in vascular smooth muscle during hypertension and metabolic disorders.Microcirculation (New York, N.Y. : 1994) · 2018Review
- The envenomation of general physiology throughout the last century.The Journal of general physiology · 2017Review
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11 authors.
Funding
Abstract
Electrically excitable cells, such as neurons, exhibit tremendous diversity in their firing patterns, a consequence of the complex collection of ion channels present in any specific cell. Although numerous methods are capable of measuring cellular electrical signals, understanding which types of ion channels give rise to these signals remains a significant challenge. Here, we describe exogenous probes which use a novel mechanism to report activity of voltage-gated channels. We have synthesized chemoselective derivatives of the tarantula toxin guangxitoxin-1E (GxTX), an inhibitory cystine knot peptide that binds selectively to Kv2-type voltage gated potassium channels. We find that voltage activation of Kv2.1 channels triggers GxTX dissociation, and thus GxTX binding dynamically marks Kv2 activation. We identify GxTX residues that can be replaced by thiol- or alkyne-bearing amino acids, without disrupting toxin folding or activity, and chemoselectively ligate fluorophores or affinity probes to these sites. We find that GxTX-fluorophore conjugates colocalize with Kv2.1 clusters in live cells and are released from channels activated by voltage stimuli. Kv2.1 activation can be detected with concentrations of probe that have a trivial impact on cellular currents. Chemoselective GxTX mutants conjugated to dendrimeric beads likewise bind live cells expressing Kv2.1, and the beads are released by channel activation. These optical sensors of conformational change are prototype probes that can indicate when ion channels contribute to electrical signaling.
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