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

Niklas Schütter,Vitya Vardanyan,Sérgio Marangoni,Cháriston André Dal Belo,Olaf Pongs,Stephen Hyslop,Sönke Hornig,Yuri Correia Barreto,Léa Rodrigues-Simioni

doi:10.3390/toxins11060335

Abstract

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.

Highlights

Voltage-gated potassium (Kv) channels play an important role in controlling neuronal excitability [1,2]
Since no further inhibition was observed with the application of a higher concentration (2.4 μM) of MiDCA1 in dorsal root ganglion (DRG) neurons, we chose to use a concentration of 1 μM to economize on the limited amount of toxin available
Our results show that MiDCA1 inhibits Kv2.1 potassium channels

Summary

Introduction

Voltage-gated potassium (Kv) channels play an important role in controlling neuronal excitability [1,2] Inhibition of these channels leads to membrane depolarization and may result in increased neurotransmitter release at nerve terminals [3,4,5]. In the peripheral nervous system, Kv channel inhibition is associated with hyperexcitability, tissue paralysis, and potential neuronal cell death. Many venomous animals, such as marine cone snails, spiders, scorpions, sea anemones and snakes produce toxins that act on Kv channels to facilitate the capture of prey [6,7,8]. Experiments with mouse hemidiaphragm preparations have shown that, like other neurotoxic PLA2 s [15,16], MiDCA1 affects neurotransmitter release and the corresponding muscle twitch tension [13]

Methods

Results

Conclusion