Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Sci Rep
2022 Mar 30;121:5352. doi: 10.1038/s41598-022-09339-x.
Show Gene links
Show Anatomy links
Sea anemone Bartholomea annulata venom inhibits voltage-gated Na+ channels and activates GABAA receptors from mammals.
Colom-Casasnovas A
,
Garay E
,
Cisneros-Mejorado A
,
Aguilar MB
,
Lazcano-Pérez F
,
Arellano RO
,
Sánchez-Rodríguez J
.
???displayArticle.abstract???
Toxin production in nematocysts by Cnidaria phylum represents an important source of bioactive compounds. Using electrophysiology and, heterologous expression of mammalian ion channels in the Xenopus oocyte membrane, we identified two main effects produced by the sea anemone Bartholomea annulata venom. Nematocysts isolation and controlled discharge of their content, revealed that venom had potent effects on both voltage-dependent Na+ (Nav) channels and GABA type A channel receptors (GABAAR), two essential proteins in central nervous system signaling. Unlike many others sea anemone toxins, which slow the inactivation rate of Nav channels, B. annulata venom potently inhibited the neuronal action potential and the Na+ currents generated by distinct Nav channels opening, including human TTX-sensitive (hNav1.6) and TTX-insensitive Nav channels (hNav1.5). A second effect of B. annulata venom was an agonistic action on GABAAR that activated distinct receptors conformed by either α1β2γ2, α3β2γ1 or, ρ1 homomeric receptors. Since GABA was detected in venom samples by ELISA assay at low nanomolar range, it was excluded that GABA from nematocysts directly activated the GABAARs. This revealed that substances in B. annulata nematocysts generated at least two potent and novel effects on mammalian ion channels that are crucial for nervous system signaling.
Figure 8. B. annulata venom contains an agonist of GABAA receptors. (a) Traces on the left illustrate inward current responses in Xenopus oocytes expressing the neuronal GABAA (α1β2γ2) receptor; cells were held atâââ60 mV and superfused with either GABA (10 μM; black trace) or AE (1 mg mlâ1; orange trace). In the trace on the right, AE was applied close to the oocyte surface using the jet delivery method, which consists of a small volume (25â75 nl) ejected from a micropipette filled with solution containing AE (0.5 mg mlâ1), four AE-jets (orange arrows) applied successively show that current responses generated were robust and reproducible. (b) Top traces show that native oocytes (H2O-injected) were not sensitive to GABA superfusion or to AE jet-delivery (orange arrow indicates jet activation), while oocytes from the same frog expressing the neuronal GABAA receptor (bottom traces) generated robust current responses to both GABA and AE. (c) Traces are responses at different holding potentials fromâââ100 toâ+â40 mV elicited either by jets of AE or NE as indicated; the graph is the currentâvoltage relationship of the responses by AE applying the same protocol in 6 different oocytes (2 frogs); individual data points are the meanâ±âS.D. of the peak current response in each potential. (d,e) AE (and NE) affects two more GABAA receptor types expressed in oocytes, the oligodendroglial receptor α3β2γ1 (red traces) and the homomeric Ï1 receptor (green traces). Traces in (d) show the current response to GABA around the concentration threshold for each receptor, 1 μM for α3β2γ1 and 10 nM for the Ï1 receptor. In (e) the traces on the left illustrate responses elicited by a maximal concentration of GABA in oocytes expressing the α3β2γ1 receptor (in red) or the Ï1 receptor (trace in green), while the traces to the right show the response in the respective oocytes elicited by the same dose of AE. Traces are representative of results obtained in 7 oocytes from 3 different frogs.
Ahern,
The hitchhiker's guide to the voltage-gated sodium channel galaxy.
2016, Pubmed
Ahern,
The hitchhiker's guide to the voltage-gated sodium channel galaxy.
2016,
Pubmed
Ames,
Cassiosomes are stinging-cell structures in the mucus of the upside-down jellyfish Cassiopea xamachana.
2020,
Pubmed
Anderluh,
Cytolytic peptide and protein toxins from sea anemones (Anthozoa: Actiniaria).
2002,
Pubmed
Aneiros,
A potassium channel toxin from the secretion of the sea anemone Bunodosoma granulifera. Isolation, amino acid sequence and biological activity.
1993,
Pubmed
Arellano,
Axon-to-Glia Interaction Regulates GABAA Receptor Expression in Oligodendrocytes.
2016,
Pubmed
Arellano,
Ion channels and membrane receptors in follicle-enclosed Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Arellano,
Novel Cl- currents elicited by follicle stimulating hormone and acetylcholine in follicle-enclosed Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Arellano,
Agonist-activated Ca2+ influx and Ca2+ -dependent Cl- channels in Xenopus ovarian follicular cells: functional heterogeneity within the cell monolayer.
2012,
Pubmed
,
Xenbase
Barres,
Cell death and control of cell survival in the oligodendrocyte lineage.
1992,
Pubmed
Beckmann,
The nematocyst: a molecular map of the cnidarian stinging organelle.
2012,
Pubmed
Béress,
Purification and characterisation of four polypeptides with neurotoxic activity from Condylactis aurantiaca.
1976,
Pubmed
Béress,
Purification of three polypeptides with neuro- and cardiotoxic activity from the sea anemone Anemonia sulcata.
1975,
Pubmed
Bernaldez,
Electrophysiological characterization of a novel small peptide from the venom of Conus californicus that targets voltage-gated neuronal Ca2+ channels.
2011,
Pubmed
,
Xenbase
Bloom,
Partial purification of box jellyfish (Chironex fleckeri) nematocyst venom isolated at the beachside.
1998,
Pubmed
Brinkman,
Venom proteome of the box jellyfish Chironex fleckeri.
2012,
Pubmed
Bruhn,
Isolation and characterisation of five neurotoxic and cardiotoxic polypeptides from the sea anemone Anthopleura elegantissima.
2001,
Pubmed
Castañeda,
Characterization of a potassium channel toxin from the Caribbean Sea anemone Stichodactyla helianthus.
1995,
Pubmed
Catterall,
Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore.
1978,
Pubmed
Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed
Cisneros-Mejorado,
Demyelination-Remyelination of the Rat Caudal Cerebellar Peduncle Evaluated with Magnetic Resonance Imaging.
2020,
Pubmed
Columbus-Shenkar,
Dynamics of venom composition across a complex life cycle.
2018,
Pubmed
D'Ambra,
A Review of Toxins from Cnidaria.
2020,
Pubmed
Diaz-Garcia,
Toxins from Physalia physalis (Cnidaria) raise the intracellular Ca(2+) of beta-cells and promote insulin secretion.
2012,
Pubmed
Dudley,
mu-conotoxin GIIIA interactions with the voltage-gated Na(+) channel predict a clockwise arrangement of the domains.
2000,
Pubmed
Dumont,
Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
1972,
Pubmed
,
Xenbase
Fautin,
Structural diversity, systematics, and evolution of cnidae.
2009,
Pubmed
Frazão,
Sea anemone (Cnidaria, Anthozoa, Actiniaria) toxins: an overview.
2012,
Pubmed
Grajales,
Elucidating the evolutionary relationships of the Aiptasiidae, a widespread cnidarian-dinoflagellate model system (Cnidaria: Anthozoa: Actiniaria: Metridioidea).
2016,
Pubmed
Gundersen,
Voltage-operated channels induced by foreign messenger RNA in Xenopus oocytes.
1983,
Pubmed
,
Xenbase
Gundersen,
Messenger RNA from human brain induces drug- and voltage-operated channels in Xenopus oocytes.
NULL,
Pubmed
,
Xenbase
Hernandez-Plata,
Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer.
2012,
Pubmed
Honma,
Peptide toxins in sea anemones: structural and functional aspects.
2006,
Pubmed
Israel,
Toxins as tools: Fingerprinting neuronal pharmacology.
2018,
Pubmed
Israel,
Sodium Channels and Venom Peptide Pharmacology.
2017,
Pubmed
Johnston,
Muscimol as an ionotropic GABA receptor agonist.
2014,
Pubmed
Jouiaei,
Ancient Venom Systems: A Review on Cnidaria Toxins.
2015,
Pubmed
Kozlov,
Animal toxins for channelopathy treatment.
2018,
Pubmed
Kubota,
Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin.
2017,
Pubmed
Kudryavtsev,
Neurotoxins from snake venoms and α-conotoxin ImI inhibit functionally active ionotropic γ-aminobutyric acid (GABA) receptors.
2015,
Pubmed
,
Xenbase
Lazcano-Pérez,
Electrophysiological activity of a neurotoxic fraction from the venom of box jellyfish Carybdea marsupialis.
2017,
Pubmed
,
Xenbase
Lazcano-Pérez,
A purified Palythoa venom fraction delays sodium current inactivation in sympathetic neurons.
2014,
Pubmed
Lazcano-Pérez,
Cnidarian Neurotoxic Peptides Affecting Central Nervous System Targets.
2016,
Pubmed
Lee,
Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxin.
2008,
Pubmed
Liao,
Cnidarian peptide neurotoxins: a new source of various ion channel modulators or blockers against central nervous systems disease.
2019,
Pubmed
Macrander,
Tissue-Specific Venom Composition and Differential Gene Expression in Sea Anemones.
2016,
Pubmed
Madio,
Revisiting venom of the sea anemone Stichodactyla haddoni: Omics techniques reveal the complete toxin arsenal of a well-studied sea anemone genus.
2017,
Pubmed
Madio,
Sea Anemone Toxins: A Structural Overview.
2019,
Pubmed
Marino,
Effect of various factors on Pelagia noctiluca (Cnidaria, Scyphozoa) crude venom-induced haemolysis.
2008,
Pubmed
Martinez-Torres,
Expression of gamma-aminobutyric acid rho 1 and rho 1 Delta 450 as gene fusions with the green fluorescent protein.
2001,
Pubmed
,
Xenbase
Morabito,
Nematocytes' activation in Pelagia noctiluca (Cnidaria, Scyphozoa) oral arms.
2012,
Pubmed
Morabito,
Crude venom from nematocysts of Pelagia noctiluca (Cnidaria: Scyphozoa) elicits a sodium conductance in the plasma membrane of mammalian cells.
2017,
Pubmed
Moran,
Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones.
2012,
Pubmed
Moran,
Sea anemone toxins affecting voltage-gated sodium channels--molecular and evolutionary features.
2009,
Pubmed
Narahashi,
Chemicals as tools in the study of excitable membranes.
1974,
Pubmed
Nesher,
The sea anemone toxin AdE-1 modifies both sodium and potassium currents of rat cardiomyocytes.
2014,
Pubmed
Nesher,
AdE-1, a new inotropic Na(+) channel toxin from Aiptasia diaphana, is similar to, yet distinct from, known anemone Na(+) channel toxins.
2013,
Pubmed
Norton,
Structures of sea anemone toxins.
2009,
Pubmed
Ordaz,
GABAA Receptors Expressed in Oligodendrocytes Cultured from the Neonatal Rat Contain α3 and γ1 Subunits and Present Differential Functional and Pharmacological Properties.
2021,
Pubmed
,
Xenbase
Parker,
Activation of a common effector system by different brain neurotransmitter receptors in Xenopus oocytes.
1987,
Pubmed
,
Xenbase
Pérez-Samartín,
Inwardly Rectifying K+ Currents in Cultured Oligodendrocytes from Rat Optic Nerve are Insensitive to pH.
2017,
Pubmed
,
Xenbase
Ravindran,
Biological activity of sea anemone proteins: I. Toxicity and histopathology.
2010,
Pubmed
Remigante,
Impact of Scyphozoan Venoms on Human Health and Current First Aid Options for Stings.
2018,
Pubmed
Restano-Cassulini,
Antivenom Evaluation by Electrophysiological Analysis.
2017,
Pubmed
Rodríguez,
Peptide fingerprinting of the neurotoxic fractions isolated from the secretions of sea anemones Stichodactyla helianthus and Bunodosoma granulifera. New members of the APETx-like family identified by a 454 pyrosequencing approach.
2012,
Pubmed
Sánchez-Rodríguez,
Isolation, partial purification and characterization of active polypeptide from the sea anemone Bartholomea annulata.
2006,
Pubmed
Scappaticci,
NMDA and GABA B receptors are involved in controlling nematocyst discharge in hydra.
2008,
Pubmed
Ständker,
A new toxin from the sea anemone Condylactis gigantea with effect on sodium channel inactivation.
2006,
Pubmed
Torres,
Electrophysiological and hemolytic activity elicited by the venom of the jellyfish Cassiopea xamachana.
2001,
Pubmed
,
Xenbase
Zaharenko,
Characterization of selectivity and pharmacophores of type 1 sea anemone toxins by screening seven Na(v) sodium channel isoforms.
2012,
Pubmed
