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dc.creatorRosso Julien, Jean Pierre
dc.creatorSchwarz, Jürgen R.
dc.creatorDiaz Bustamante, Marcelo
dc.creatorCéard, Brigitte
dc.creatorGutiérrez, José María
dc.creatorKneussel, Matthias
dc.creatorPongs, Olaf
dc.creatorBosmans, Frank
dc.creatorBougis, Pierre Edouard
dc.date.accessioned2017-07-07T18:49:35Z
dc.date.available2017-07-07T18:49:35Z
dc.date.issued2015-02-24
dc.identifier.citationhttp://www.pnas.org/content/112/8/E891
dc.identifier.issn1091-6490
dc.identifier.urihttps://hdl.handle.net/10669/30341
dc.description.abstractGABAA 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.es_ES
dc.language.isoen_USes_ES
dc.sourceProceedings of the National Academy of Sciences of the United States of America; Volumen 112, Número 8. 2015es_ES
dc.subjectCoral snake toxines_ES
dc.subjectMmTX1es_ES
dc.subjectMmTX2es_ES
dc.subjectGABA(A) receptores_ES
dc.subjectHippocampal neuronses_ES
dc.titleMmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activityes_ES
dc.typeartículo científico
dc.identifier.doi10.1073/pnas.1415488112
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.identifier.pmid25675485
dc.identifier.pmidPMC4345566


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