The action of Con-ikot-ikot toxin on single AMPA-type glutamate receptors
| Autor: | Miriam Chebli, Jelena Baranovic, Andrew J.R. Plested, Sebastian Braunbeck, Zaki N, Minniberger S |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Physiology
Glutamic Acid AMPA receptor Neurotransmission Ion Channels 03 medical and health sciences 0302 clinical medicine Desensitization (telecommunications) Conus Conotoxin Receptors AMPA AMPA receptors alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Ion channel 030304 developmental biology 0303 health sciences biology patch-clamp electrophyioslogy Chemistry Glutamate receptor ion channels biology.organism_classification 3. Good health Receptors Glutamate nervous system Biophysics Excitatory postsynaptic potential conotoxin single-channel recordings 030217 neurology & neurosurgery |
| Zdroj: | Baranovic, J, Braunbeck, S, Zaki, N, Minniberger, S, Chebli, M & Plested, A 2022, ' The action of Con-ikot-ikot toxin on single AMPA-type glutamate receptors ', Journal of General Physiology, vol. 154, no. 5, e202112912 . https://doi.org/10.1085/jgp.202112912 bioRxiv |
| DOI: | 10.1085/jgp.202112912 |
| Popis: | SummaryConotoxins are a large group of naturally occurring toxic peptides produced by the predatory sea snails of the genus Conus. Many of these toxins target ion channels, often with high specificity and affinity. As such, they have proven to be invaluable for basic research as well as acting as leads for therapeutic strategies. Con-ikot-ikot is the only conotoxin so far identified that targets AMPA-type glutamate receptors, the main mediators of excitatory neurotransmission in the vertebrate brain. Here, we describe how the toxin modifies the activity of AMPA receptors at the single-channel level. The toxin binds to the AMPA receptor with high affinity (EC50 = 5 nM) and once bound, takes minutes to wash out. As shown previously, it effectively blocks desensitization of AMPA receptors, however, compared to other desensitisation blockers, it is a poor stabiliser of the open channel because toxin-bound AMPA receptors undergo frequent, brief closures. We propose this is a direct consequence of the toxin’s unique binding mode to the ligand binding domains. Unlike other blockers of desensitization, which stabilise individual dimers within an AMPA receptor tetramer, the toxin immobilizes all four ligand binding domains of the tetramer. This result further emphasises that quaternary reorganization of independent LBD dimers is essential for the full activity of AMPA receptors. |
| Databáze: | OpenAIRE |
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