MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity

Standard

MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity. / Rosso, Jean-Pierre; Schwarz, Juergen; Diaz-Bustamante, Marcelo; Céard, Brigitte; Gutiérrez, José M; Kneussel, Matthias; Pongs, Olaf; Bosmans, Frank; Bougis, Pierre E.

In: P NATL ACAD SCI USA, Vol. 112, No. 8, 24.02.2015, p. E891-900.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Rosso, J-P, Schwarz, J, Diaz-Bustamante, M, Céard, B, Gutiérrez, JM, Kneussel, M, Pongs, O, Bosmans, F & Bougis, PE 2015, 'MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity', P NATL ACAD SCI USA, vol. 112, no. 8, pp. E891-900. https://doi.org/10.1073/pnas.1415488112

APA

Rosso, J-P., Schwarz, J., Diaz-Bustamante, M., Céard, B., Gutiérrez, J. M., Kneussel, M., Pongs, O., Bosmans, F., & Bougis, P. E. (2015). MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity. P NATL ACAD SCI USA, 112(8), E891-900. https://doi.org/10.1073/pnas.1415488112

Vancouver

Rosso J-P, Schwarz J, Diaz-Bustamante M, Céard B, Gutiérrez JM, Kneussel M et al. MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity. P NATL ACAD SCI USA. 2015 Feb 24;112(8):E891-900. https://doi.org/10.1073/pnas.1415488112

Bibtex

@article{14a17d3b8b3245d98c9d7c87baf11355,
title = "MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity",
abstract = "GABAA receptors shape synaptic transmission by modulating Cl(-) conductance across the cell membrane. Remarkably, animal toxins that specifically target GABAA 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 GABAA 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 GABAA receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the α(+)/β(-) 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 = "Jean-Pierre Rosso and Juergen Schwarz and Marcelo Diaz-Bustamante and Brigitte C{\'e}ard and Guti{\'e}rrez, {Jos{\'e} M} and Matthias Kneussel and Olaf Pongs and Frank Bosmans and Bougis, {Pierre E}",
year = "2015",
month = feb,
day = "24",
doi = "10.1073/pnas.1415488112",
language = "English",
volume = "112",
pages = "E891--900",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "8",

}

RIS

TY - JOUR

T1 - MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity

AU - Rosso, Jean-Pierre

AU - Schwarz, Juergen

AU - Diaz-Bustamante, Marcelo

AU - Céard, Brigitte

AU - Gutiérrez, José M

AU - Kneussel, Matthias

AU - Pongs, Olaf

AU - Bosmans, Frank

AU - Bougis, Pierre E

PY - 2015/2/24

Y1 - 2015/2/24

N2 - GABAA receptors shape synaptic transmission by modulating Cl(-) conductance across the cell membrane. Remarkably, animal toxins that specifically target GABAA 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 GABAA 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 GABAA receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the α(+)/β(-) 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.

AB - GABAA receptors shape synaptic transmission by modulating Cl(-) conductance across the cell membrane. Remarkably, animal toxins that specifically target GABAA 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 GABAA 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 GABAA receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the α(+)/β(-) 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.

U2 - 10.1073/pnas.1415488112

DO - 10.1073/pnas.1415488112

M3 - SCORING: Journal article

C2 - 25675485

VL - 112

SP - E891-900

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 8

ER -