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Abstract
GABA(A) receptors shape synaptic transmission by modulating Cl-conductance across the cell membrane. Remarkably, animal toxins that specifically target GABA(A) receptors have not been identified. Here, we report the discovery of micrurotoxin1 (MmTX1) and MmTX2, two toxins present in Costa Rican coral snake venom that tightly bind to GABA(A) receptors at subnanomolar concentrations. Studies with recombinant and synthetic toxin variants on hippocampal neurons and cells expressing common receptor compositions suggest that MmTX1 and MmTX2 allosterically increase GABA(A) receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the alpha(+)/beta(-) interface. Moreover, hippocampal neuron excitability measurements reveal toxin-induced transitory network inhibition, followed by an increase in spontaneous activity. In concert, toxin injections into mouse brain result in reduced basal activity between intense seizures. Altogether, we characterized two animal toxins that enhance GABAA receptor sensitivity to agonist, thereby establishing a previously unidentified class of tools to study this receptor family.
Keywords
coral snake toxin, MmTX1, MmTX2, GABA(A) receptor, hippocampal neurons, NICOTINIC ACETYLCHOLINE-RECEPTORS, AMINO-ACID-SEQUENCE, BETA-SUBUNIT, RAT-BRAIN, ALPHA-BUNGAROTOXIN, PHARMACOLOGY, BINDING, NEUROTOXINS, SUBTYPES, NEURONS

Citation

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MLA
Rosso, Jean-Pierre, Jürgen R Schwarz, Marcelo Diaz-Bustamante, et al. “MmTX1 and MmTX2 from Coral Snake Venom Potently Modulate GABAa Receptor Activity.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112.8 (2015): E891–E900. Print.
APA
Rosso, J.-P., Schwarz, J. R., Diaz-Bustamante, M., Céard, B., Gutiérrez, J. M., Kneussel, M., Pongs, O., et al. (2015). MmTX1 and MmTX2 from coral snake venom potently modulate GABAa receptor activity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 112(8), E891–E900.
Chicago author-date
Rosso, Jean-Pierre, Jürgen R Schwarz, Marcelo Diaz-Bustamante, Brigitte Céard, José M Gutiérrez, Matthias Kneussel, Olaf Pongs, Frank Bosmans, and Pierre E Bougis. 2015. “MmTX1 and MmTX2 from Coral Snake Venom Potently Modulate GABAa Receptor Activity.” Proceedings of the National Academy of Sciences of the United States of America 112 (8): E891–E900.
Chicago author-date (all authors)
Rosso, Jean-Pierre, Jürgen R Schwarz, Marcelo Diaz-Bustamante, Brigitte Céard, José M Gutiérrez, Matthias Kneussel, Olaf Pongs, Frank Bosmans, and Pierre E Bougis. 2015. “MmTX1 and MmTX2 from Coral Snake Venom Potently Modulate GABAa Receptor Activity.” Proceedings of the National Academy of Sciences of the United States of America 112 (8): E891–E900.
Vancouver
1.
Rosso J-P, Schwarz JR, Diaz-Bustamante M, Céard B, Gutiérrez JM, Kneussel M, et al. MmTX1 and MmTX2 from coral snake venom potently modulate GABAa receptor activity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2015;112(8):E891–E900.
IEEE
[1]
J.-P. Rosso et al., “MmTX1 and MmTX2 from coral snake venom potently modulate GABAa receptor activity,” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 112, no. 8, pp. E891–E900, 2015.
@article{8584517,
  abstract     = {{GABA(A) receptors shape synaptic transmission by modulating Cl-conductance across the cell membrane. Remarkably, animal toxins that specifically target GABA(A) receptors have not been identified. Here, we report the discovery of micrurotoxin1 (MmTX1) and MmTX2, two toxins present in Costa Rican coral snake venom that tightly bind to GABA(A) receptors at subnanomolar concentrations. Studies with recombinant and synthetic toxin variants on hippocampal neurons and cells expressing common receptor compositions suggest that MmTX1 and MmTX2 allosterically increase GABA(A) receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the alpha(+)/beta(-) interface. Moreover, hippocampal neuron excitability measurements reveal toxin-induced transitory network inhibition, followed by an increase in spontaneous activity. In concert, toxin injections into mouse brain result in reduced basal activity between intense seizures. Altogether, we characterized two animal toxins that enhance GABAA receptor sensitivity to agonist, thereby establishing a previously unidentified class of tools to study this receptor family.}},
  author       = {{Rosso, Jean-Pierre and Schwarz, Jürgen R and Diaz-Bustamante, Marcelo and Céard, Brigitte and Gutiérrez, José M and Kneussel, Matthias and Pongs, Olaf and Bosmans, Frank and Bougis, Pierre E}},
  issn         = {{0027-8424}},
  journal      = {{PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}},
  keywords     = {{coral snake toxin,MmTX1,MmTX2,GABA(A) receptor,hippocampal neurons,NICOTINIC ACETYLCHOLINE-RECEPTORS,AMINO-ACID-SEQUENCE,BETA-SUBUNIT,RAT-BRAIN,ALPHA-BUNGAROTOXIN,PHARMACOLOGY,BINDING,NEUROTOXINS,SUBTYPES,NEURONS}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{E891--E900}},
  title        = {{MmTX1 and MmTX2 from coral snake venom potently modulate GABAa receptor activity}},
  url          = {{http://dx.doi.org/10.1073/pnas.1415488112}},
  volume       = {{112}},
  year         = {{2015}},
}

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