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Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA(2)-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom

MiDCA1, a phospholipase A(2) (PLA(2)) neurotoxin isolated from Micrurus dumerilii carinicauda coral snake venom, inhibited a major component of voltage-activated potassium (Kv) currents (41 ± 3% inhibition with 1 μM toxin) in mouse cultured dorsal root ganglion (DRG) neurons. In addition, the select...

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Detalles Bibliográficos
Autores principales: Schütter, Niklas, Barreto, Yuri Correia, Vardanyan, Vitya, Hornig, Sönke, Hyslop, Stephen, Marangoni, Sérgio, Rodrigues-Simioni, Léa, Pongs, Olaf, Dal Belo, Cháriston André
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628393/
https://www.ncbi.nlm.nih.gov/pubmed/31212818
http://dx.doi.org/10.3390/toxins11060335
Descripción
Sumario:MiDCA1, a phospholipase A(2) (PLA(2)) neurotoxin isolated from Micrurus dumerilii carinicauda coral snake venom, inhibited a major component of voltage-activated potassium (Kv) currents (41 ± 3% inhibition with 1 μM toxin) in mouse cultured dorsal root ganglion (DRG) neurons. In addition, the selective Kv2.1 channel blocker guangxitoxin (GxTx-1E) and MiDCA1 competitively inhibited the outward potassium current in DRG neurons. MiDCA1 (1 µM) reversibly inhibited the Kv2.1 current by 55 ± 8.9% in a Xenopus oocyte heterologous system. The toxin showed selectivity for Kv2.1 channels over all the other Kv channels tested in this study. We propose that Kv2.1 channel blockade by MiDCA1 underlies the toxin’s action on acetylcholine release at mammalian neuromuscular junctions.