ArticleThe Journal of biological chemistry2010
Target promiscuity and heterogeneous effects of tarantula venom peptides affecting Na+ and K+ ion channels.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 93 citations in OpenAlex.
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- Spider venom peptides with unique fold selectively block Shaker-type potassium channels.Cellular and molecular life sciences : CMLS · 2025Article
- Modulation of human dorsal root ganglion neuron firing by the Nav1.8 inhibitor suzetrigine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Neurotoxins Acting on TRPV1-Building a Molecular Template for the Study of Pain and Thermal Dysfunctions.Toxins · 2025Review
- Piezo1 and tissue fibrosis: insights into its role and potential for modulation.Burns & trauma · 2025Review
- Pharmacology of PIEZO1 channels.British journal of pharmacology · 2024Review
- Optimizing Nav1.7-Targeted Analgesics: Revealing Off-Target Effects of Spider Venom-Derived Peptide Toxins and Engineering Strategies for Improvement.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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- Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Pharmacological Inhibition of the Voltage-Gated Sodium Channel NaACS pharmacology & translational science · 2021Article
- Mechanotransduction channel Piezo is widely expressed in the spider, Cupiennius salei, mechanosensory neurons and central nervous system.Scientific reports · 2021Article
- Pain-related toxins in scorpion and spider venoms: a face to face with ion channels.The journal of venomous animals and toxins including tropical diseases · 2021Review
- Venom-Derived Peptides Inhibiting Voltage-Gated Sodium and Calcium Channels in Mammalian Sensory Neurons.Advances in experimental medicine and biology · 2021Article
- Peptide Toxins Targeting KV Channels.Handbook of experimental pharmacology · 2021Review
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- Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways.Toxins · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Venom-derived peptide modulators of ion channel gating are regarded as essential tools for understanding the molecular motions that occur during the opening and closing of ion channels. In this study, we present the characterization of five spider toxins on 12 human voltage-gated ion channels, following observations about the target promiscuity of some spider toxins and the ongoing revision of their "canonical" gating-modifying mode of action. The peptides were purified de novo from the venom of Grammostola rosea tarantulas, and their sequences were confirmed by Edman degradation and mass spectrometry analysis. Their effects on seven tetrodotoxin-sensitive Na(+) channels, the three human ether-à-go-go (hERG)-related K(+) channels, and two human Shaker-related K(+) channels were extensively characterized by electrophysiological techniques. All the peptides inhibited ion conduction through all the Na(+) channels tested, although with distinctive patterns. The peptides also affected the three pharmaceutically relevant hERG isoforms differently. At higher concentrations, all peptides also modified the gating of the Na(+) channels by shifting the activation to more positive potentials, whereas more complex effects were recorded on hERG channels. No effects were evident on the two Shaker-related K(+) channels at concentrations well above the IC(50) value for the affected channels. Given the sequence diversity of the tested peptides, we propose that tarantula toxins should be considered both as multimode and target-promiscuous ion channel modulators; both features should not be ignored when extracting mechanistic interpretations about ion channel gating. Our observations could also aid in future structure-function studies and might help the development of novel ion channel-specific drugs.
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Registered trials
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.