Special Issue "Toxins and Ion Channels"

A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: closed (30 April 2018) | Viewed by 9578

Special Issue Editors

Dr. Evelyne Benoit
E-Mail Website
Guest Editor
CEA, Institut des Sciences du Vivant Frédéric Joliot, Département Médicaments et Technologies pour la Santé (DMTS), Service d’Ingénierie Moléculaire pour la Santé (SIMoS), Université Paris-Saclay, ERL 9004 CNRS/CEA, F-91191 Gif sur Yvette, France
Interests: toxins; voltage-gated sodium channels; voltage-gated potassium channels; voltage-gated calcium channels; nicotinic acetylcholine receptors; venom toxins; marine toxins; bacterial toxins
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jordi Molgó
E-Mail Website
Guest Editor
CEA, INRAE, Institut des Sciences du Vivant Frédéric Joliot, Département Médicaments et Technologies pour la Santé (DMTS), Equipe de Recherche Labellisée CNRS n° 9004, Service d’Ingénierie Moléculaire pour la Santé (SIMoS), Université Paris-Saclay, Bâtiment 152, Point courrier 24, F-91191 Gif sur Yvette, France
Interests: natural toxins from marine and terrestrial organisms; voltage-gated ion channels; nicotinic acetylcholine receptors; cholinesterases; IP3 receptors; cell signaling; synaptic transmission; neuromuscular transmission; transmitter release
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Toxins are usually potent and selective for a given molecular target, and have been frequently used as probes of the structure and function of voltage-gated and ligand-gated ion channels. For these reasons, toxins are of substantial interest, as both pharmacological tools and therapeutic leads. They are, thus, particularly interesting for the pharmaceutical industry. Numerous ion channels constitute important targets for the treatment of neurological or cardiovascular diseases. In addition, the ligand-gated ion channels including nicotinic acetylcholine (nAChR), serotonin type 3 (5-HT3R), γ-aminobutyric acid (GABAAR), and glycine (GlyR) receptors are of great physiological relevance in many neurological disease pathways. In this Special Issue we welcome papers dealing with new toxins and/or new targets from natural sources or from engineering (chemical or recombinant synthesis). Emphasis on toxin-induced biophysical and pharmacological channel modulation, as well as modeling of toxin-target interactions, will be highly appreciated. Additionally, the selection of toxins with well-characterized mode and mechanism of action is relevant, since these toxins may provide scaffolds for drug design studies and will advance our knowledge and understanding of ion channels in common or neglected diseases.

Dr. Evelyne BENOIT
Dr. Jordi MOLGO
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Toxins and voltage-gated ion channels
  • Toxins and ligand-gated channels
  • New toxins
  • New toxin target(s)
  • Natural and synthetic toxins
  • Toxin engineering
  • Toxin high-throughput screening
  • Toxins and channel modulation
  • Modeling of toxin-target interactions
  • Toxins and drug discovery

Published Papers (3 papers)

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Research

Article
Synthesis, Structure and Biological Activity of CIA and CIB, Two α-Conotoxins from the Predation-Evoked Venom of Conus catus
Toxins 2018, 10(6), 222; https://doi.org/10.3390/toxins10060222 - 01 Jun 2018
Cited by 13 | Viewed by 2892
Abstract
Cone snails produce a fast-acting and often paralyzing venom that is usually injected into their prey or predator through a hypodermic needle-like modified radula tooth. Many diverse compounds are found in their venom including small molecules, peptides and enzymes. However, peptidic toxins called [...] Read more.
Cone snails produce a fast-acting and often paralyzing venom that is usually injected into their prey or predator through a hypodermic needle-like modified radula tooth. Many diverse compounds are found in their venom including small molecules, peptides and enzymes. However, peptidic toxins called conotoxins (10–40 residues and 2–4 disulfide bonds) largely dominate these cocktails. These disulfide rich toxins are very valuable pharmacological tools for investigating the function of ions channels, G-protein coupled receptors, transporters and enzymes. Here, we report on the synthesis, structure determination and biological activities of two α-conotoxins, CIA and CIB, found in the predatory venom of the piscivorous species Conus catus. CIA is a typical 3/5 α-conotoxin that blocks the rat muscle type nAChR with an IC50 of 5.7 nM. Interestingly, CIA also inhibits the neuronal rat nAChR subtype α3β2 with an IC50 of 2.06 μM. CIB is a 4/7 α-conotoxin that blocks rat neuronal nAChR subtypes, including α3β2 (IC50 = 128.9 nM) and α7 (IC50 = 1.51 μM). High resolution NMR structures revealed typical α-conotoxin folds for both peptides. We also investigated the in vivo effects of these toxins on fish, since both peptides were identified in the predatory venom of C. catus. Consistent with their pharmacology, CIA was highly paralytic to zebrafish (ED50 = 110 μg/kg), whereas CIB did not affect the mobility of the fish. In conclusion, CIA likely participates in prey capture through muscle paralysis, while the putative ecological role of CIB remains to be elucidated. Full article
(This article belongs to the Special Issue Toxins and Ion Channels)
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Article
Selective Closed-State Nav1.7 Blocker JZTX-34 Exhibits Analgesic Effects against Pain
Toxins 2018, 10(2), 64; https://doi.org/10.3390/toxins10020064 - 02 Feb 2018
Cited by 15 | Viewed by 2825
Abstract
Jingzhaotoxin-34 (JZTX-34) is a selective inhibitor of tetrodotoxin-sensitive (TTX-S) sodium channels. In this study, we found that JZTX-34 selectively acted on Nav1.7 with little effect on other sodium channel subtypes including Nav1.5. If the DIIS3-S4 linker of Nav1.5 is substituted by the correspond [...] Read more.
Jingzhaotoxin-34 (JZTX-34) is a selective inhibitor of tetrodotoxin-sensitive (TTX-S) sodium channels. In this study, we found that JZTX-34 selectively acted on Nav1.7 with little effect on other sodium channel subtypes including Nav1.5. If the DIIS3-S4 linker of Nav1.5 is substituted by the correspond linker of Nav1.7, the sensitivity of Nav1.5 to JZTX-34 extremely increases to 1.05 µM. Meanwhile, a mutant D816R in the DIIS3-S4 linker of Nav1.7 decreases binding affinity of Nav1.7 to JZTX-34 about 32-fold. The reverse mutant R800D at the corresponding position in Nav1.5 greatly increased its binding affinity to JZTX-34. This implies that JZTX-34 binds to DIIS3-S4 linker of Nav1.7 and the critical residue of Nav1.7 is D816. Unlike β-scorpion toxin trapping sodium channel in an open state, activity of JZTX-34 requires the sodium channel to be in a resting state. JZTX-34 exhibits an obvious analgesic effect in a rodent pain model. Especially, it shows a longer duration and is more effective than morphine in hot pain models. In a formalin-induced pain model, JZTX-34 at dose of 2 mg/kg is equipotent with morphine (5 mg/kg) in the first phase and several-fold more effective than morphine in second phase. Taken together, our data indicate that JZTX-34 releases pain by selectively binding to the domain II voltage sensor of Nav1.7 in a closed configuration. Full article
(This article belongs to the Special Issue Toxins and Ion Channels)
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Article
P2X-Receptor Antagonists Inhibit the Interaction of S. aureus Hemolysin A with Membranes
Toxins 2017, 9(10), 332; https://doi.org/10.3390/toxins9100332 - 19 Oct 2017
Cited by 9 | Viewed by 3180
Abstract
The pore forming hemolysin A, Hla, is a major virulence factor of Staphylococcus aureus. Apparently, 1–2 pore(s) per cell suffice(s) to cause cell death. Accumulated experimental evidence points towards a major role of ATP-gated purinergic receptors (P2XR) for hemolysis caused by Hla, [...] Read more.
The pore forming hemolysin A, Hla, is a major virulence factor of Staphylococcus aureus. Apparently, 1–2 pore(s) per cell suffice(s) to cause cell death. Accumulated experimental evidence points towards a major role of ATP-gated purinergic receptors (P2XR) for hemolysis caused by Hla, complement and other pore forming proteins, presumably by increasing membrane permeability. Indeed, in experiments employing rabbit erythrocytes, inhibitory concentrations of frequently employed P2XR-antagonists were in a similar range as previously reported for erythrocytes of other species and other toxins. However, Hla-dependent hemolysis was not enhanced by extracellular ATP, and oxidized adenosinetriphosphate (oxATP) had only a minor inhibitory effect. Unexpectedly, P2XR-inhibitors also prevented Hla-induced lysis of pure lipid membranes, demonstrating that the inhibition did not even depend on the presence of P2XR. Fluorescence microscopy and gel-electrophoresis clearly revealed that P2XR-inhibitors interfere with binding and subsequent oligomerisation of Hla with membranes. Similar results were obtained employing HaCaT-cells. Furthermore, calorimetric data and hemolysis experiments with Hla pre-treated with pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) showed that this compound directly binds to Hla. Our results call for a critical re-assessment of the appealing concept, which suggests that P2XR are general amplifiers of damage by pore-forming proteins. Full article
(This article belongs to the Special Issue Toxins and Ion Channels)
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