Inhibition of Kv2.1 Potassium Channels by MiDCA1, A Pre-Synaptically Active PLA<sub>2</sub>-Type Toxin from <i>Micrurus dumerilii carinicauda</i> Coral Snake Venom
Niklas Schütter,
Yuri Correia Barreto,
Vitya Vardanyan,
Sönke Hornig,
Stephen Hyslop,
Sérgio Marangoni,
Léa Rodrigues-Simioni,
Olaf Pongs,
Cháriston André Dal Belo
Affiliations
Niklas Schütter
Institute for Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of the Saarland, D-66421 Hamburg, Germany
Yuri Correia Barreto
Interdisciplinary Centre for Research in Biotechnology (CIPBiotec), Federal University of Pampa (UNIPAMPA), Campus São Gabriel, São Gabriel 97300-000, RS, Brazil
Vitya Vardanyan
Molecular Neuroscience Group, Institute of Molecular Biology NAS RA, Hastratyan 7, Yerevan 0014, Armenia
Sönke Hornig
Center for Molecular Neurobiology Hamburg, Experimental Neuropediatrics, UKE Hamburg, 20251 Hamburg, Germany
Stephen Hyslop
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
Sérgio Marangoni
Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Cidade Universitária Zeferino Vaz, Campinas 13083-862, SP, Brazil
Léa Rodrigues-Simioni
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
Olaf Pongs
Institute for Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of the Saarland, D-66421 Hamburg, Germany
Cháriston André Dal Belo
Interdisciplinary Centre for Research in Biotechnology (CIPBiotec), Federal University of Pampa (UNIPAMPA), Campus São Gabriel, São Gabriel 97300-000, RS, Brazil
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.
