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Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA2-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom

1
Institute for Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of the Saarland, D-66421 Hamburg, Germany
2
Interdisciplinary Centre for Research in Biotechnology (CIPBiotec), Federal University of Pampa (UNIPAMPA), Campus São Gabriel, São Gabriel 97300-000, RS, Brazil
3
Molecular Neuroscience Group, Institute of Molecular Biology NAS RA, Hastratyan 7, Yerevan 0014, Armenia
4
Center for Molecular Neurobiology Hamburg, Experimental Neuropediatrics, UKE Hamburg, 20251 Hamburg, Germany
5
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas 13083-970, SP, Brazil
6
Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Cidade Universitária Zeferino Vaz, Campinas 13083-862, SP, Brazil
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(6), 335; https://doi.org/10.3390/toxins11060335
Received: 4 April 2019 / Revised: 13 May 2019 / Accepted: 14 May 2019 / Published: 12 June 2019
(This article belongs to the Special Issue Venoms and Ion Channels)
MiDCA1, a phospholipase A2 (PLA2) 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. View Full-Text
Keywords: Micrurus dumerilii carinicauda venom; phospholipase A2 neurotoxin; mouse dorsal root ganglion neurons; Kv2 selective inhibition Micrurus dumerilii carinicauda venom; phospholipase A2 neurotoxin; mouse dorsal root ganglion neurons; Kv2 selective inhibition
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Schütter, N.; Barreto, Y.C.; Vardanyan, V.; Hornig, S.; Hyslop, S.; Marangoni, S.; Rodrigues-Simioni, L.; Pongs, O.; Dal Belo, C.A. Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA2-Type Toxin from Micrurus dumerilii carinicauda Coral Snake Venom. Toxins 2019, 11, 335.

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