scholarly journals Voltage-Gated Sodium Channels: A Prominent Target of Marine Toxins

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 562
Author(s):  
Rawan Mackieh ◽  
Rita Abou-Nader ◽  
Rim Wehbe ◽  
César Mattei ◽  
Christian Legros ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Physiological Role ◽  
Supporting Cell ◽  
Cone Snail ◽  
Marine Toxins ◽  
Marine Animals ◽  
Communication Signals ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Wide Range

Voltage-gated sodium channels (VGSCs) are considered to be one of the most important ion channels given their remarkable physiological role. VGSCs constitute a family of large transmembrane proteins that allow transmission, generation, and propagation of action potentials. This occurs by conducting Na+ ions through the membrane, supporting cell excitability and communication signals in various systems. As a result, a wide range of coordination and physiological functions, from locomotion to cognition, can be accomplished. Drugs that target and alter the molecular mechanism of VGSCs’ function have highly contributed to the discovery and perception of the function and the structure of this channel. Among those drugs are various marine toxins produced by harmful microorganisms or venomous animals. These toxins have played a key role in understanding the mode of action of VGSCs and in mapping their various allosteric binding sites. Furthermore, marine toxins appear to be an emerging source of therapeutic tools that can relieve pain or treat VGSC-related human channelopathies. Several studies documented the effect of marine toxins on VGSCs as well as their pharmaceutical applications, but none of them underlined the principal marine toxins and their effect on VGSCs. Therefore, this review aims to highlight the neurotoxins produced by marine animals such as pufferfish, shellfish, sea anemone, and cone snail that are active on VGSCs and discuss their pharmaceutical values.

scholarly journals Marine Toxins That Target Voltage-gated Sodium Channels

Marine Drugs ◽  
2006 ◽  
Vol 4 (3) ◽  
pp. 157-192 ◽  
Author(s):  
Ahmed Al-Sabi ◽  
Jeff McArthur ◽  
Vitaly Ostroumov ◽  
Robert French
Keyword(s):  
Sodium Channels ◽  
Marine Toxins ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Neurotoxic peptides from the venom of the giant Australian stinging tree

2020 ◽  
Vol 6 (38) ◽  
pp. eabb8828
Author(s):  
Edward K. Gilding ◽  
Sina Jami ◽  
Jennifer R. Deuis ◽  
Mathilde R. Israel ◽  
Peta J. Harvey ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Sodium Channels ◽  
Sensory Neurons ◽  
Convergent Evolution ◽  
3D Structure ◽  
Cone Snail ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Sensory Effects ◽  
Mammalian Skin

Stinging trees from Australasia produce remarkably persistent and painful stings upon contact of their stiff epidermal hairs, called trichomes, with mammalian skin. Dendrocnide-induced acute pain typically lasts for several hours, and intermittent painful flares can persist for days and weeks. Pharmacological activity has been attributed to small-molecule neurotransmitters and inflammatory mediators, but these compounds alone cannot explain the observed sensory effects. We show here that the venoms of Australian Dendrocnide species contain heretofore unknown pain-inducing peptides that potently activate mouse sensory neurons and delay inactivation of voltage-gated sodium channels. These neurotoxins localize specifically to the stinging hairs and are miniproteins of 4 kDa, whose 3D structure is stabilized in an inhibitory cystine knot motif, a characteristic shared with neurotoxins found in spider and cone snail venoms. Our results provide an intriguing example of inter-kingdom convergent evolution of animal and plant venoms with shared modes of delivery, molecular structure, and pharmacology.

Voltage-gated sodium channels and pain-related disorders

2016 ◽  
Vol 130 (24) ◽  
pp. 2257-2265 ◽  
Author(s):  
Alexandros H. Kanellopoulos ◽  
Ayako Matsuyama
Keyword(s):  
Sodium Channels ◽  
Protein Complexes ◽  
Transmembrane Protein ◽  
Kinetic Properties ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Wide Range ◽  
Neuronal Types ◽  
Firing Properties

Voltage-gated sodium channels (VGSCs) are heteromeric transmembrane protein complexes. Nine homologous members, SCN1A–11A, make up the VGSC gene family. Sodium channel isoforms display a wide range of kinetic properties endowing different neuronal types with distinctly varied firing properties. Among the VGSCs isoforms, Nav1.7, Nav1.8 and Nav1.9 are preferentially expressed in the peripheral nervous system. These isoforms are known to be crucial in the conduction of nociceptive stimuli with mutations in these channels thought to be the underlying cause of a variety of heritable pain disorders. This review provides an overview of the current literature concerning the role of VGSCs in the generation of pain and heritable pain disorders.

scholarly journals Insights into the origins of fish hunting in venomous cone snails from studies of Conus tessulatus

2015 ◽  
Vol 112 (16) ◽  
pp. 5087-5092 ◽  
Author(s):  
Joseph W. Aman ◽  
Julita S. Imperial ◽  
Beatrix Ueberheide ◽  
Min-Min Zhang ◽  
Manuel Aguilar ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Molecular Mechanisms ◽  
Prey Capture ◽  
Sequence Similarity ◽  
Cone Snail ◽  
Evolutionary Transitions ◽  
Voltage Gated ◽  
Channel Inactivation ◽  
Voltage Gated Sodium Channels ◽  
Cone Snails

Prey shifts in carnivorous predators are events that can initiate the accelerated generation of new biodiversity. However, it is seldom possible to reconstruct how the change in prey preference occurred. Here we describe an evolutionary “smoking gun” that illuminates the transition from worm hunting to fish hunting among marine cone snails, resulting in the adaptive radiation of fish-hunting lineages comprising ∼100 piscivorous Conus species. This smoking gun is δ-conotoxin TsVIA, a peptide from the venom of Conus tessulatus that delays inactivation of vertebrate voltage-gated sodium channels. C. tessulatus is a species in a worm-hunting clade, which is phylogenetically closely related to the fish-hunting cone snail specialists. The discovery of a δ-conotoxin that potently acts on vertebrate sodium channels in the venom of a worm-hunting cone snail suggests that a closely related ancestral toxin enabled the transition from worm hunting to fish hunting, as δ-conotoxins are highly conserved among fish hunters and critical to their mechanism of prey capture; this peptide, δ-conotoxin TsVIA, has striking sequence similarity to these δ-conotoxins from piscivorous cone snail venoms. Calcium-imaging studies on dissociated dorsal root ganglion (DRG) neurons revealed the peptide’s putative molecular target (voltage-gated sodium channels) and mechanism of action (inhibition of channel inactivation). The results were confirmed by electrophysiology. This work demonstrates how elucidating the specific interactions between toxins and receptors from phylogenetically well-defined lineages can uncover molecular mechanisms that underlie significant evolutionary transitions.

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