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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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:
Communication
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
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author Schütter, Niklas
Barreto, Yuri Correia
Vardanyan, Vitya
Hornig, Sönke
Hyslop, Stephen
Marangoni, Sérgio
Rodrigues-Simioni, Léa
Pongs, Olaf
Dal Belo, Cháriston André
author_facet Schütter, Niklas
Barreto, Yuri Correia
Vardanyan, Vitya
Hornig, Sönke
Hyslop, Stephen
Marangoni, Sérgio
Rodrigues-Simioni, Léa
Pongs, Olaf
Dal Belo, Cháriston André
author_sort Schütter, Niklas
collection PubMed
description 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.
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spelling pubmed-66283932019-07-23 Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA(2)-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom Schütter, Niklas Barreto, Yuri Correia Vardanyan, Vitya Hornig, Sönke Hyslop, Stephen Marangoni, Sérgio Rodrigues-Simioni, Léa Pongs, Olaf Dal Belo, Cháriston André Toxins (Basel) Communication 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. MDPI 2019-06-12 /pmc/articles/PMC6628393/ /pubmed/31212818 http://dx.doi.org/10.3390/toxins11060335 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Schütter, Niklas
Barreto, Yuri Correia
Vardanyan, Vitya
Hornig, Sönke
Hyslop, Stephen
Marangoni, Sérgio
Rodrigues-Simioni, Léa
Pongs, Olaf
Dal Belo, Cháriston André
Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA(2)-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom
title Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA(2)-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom
title_full Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA(2)-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom
title_fullStr Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA(2)-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom
title_full_unstemmed Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA(2)-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom
title_short Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA(2)-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom
title_sort inhibition of kv2.1 potassium channels by midca1, a pre-synaptically active pla(2)-type toxin from micrurus dumerilii carinicauda coral snake venom
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628393/
https://www.ncbi.nlm.nih.gov/pubmed/31212818
http://dx.doi.org/10.3390/toxins11060335
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