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Brevetoxin and Conotoxin Interactions with Single-Domain Voltage-Gated Sodium Channels from a Diatom and
Ping Yates1, Julie A Koester1, Alison R Taylor1
1Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, NC 28403, USA.
Abstract:
The recently characterized single-domain voltage-gated ion channels from eukaryotic protists (EukCats) provide an array of novel channel proteins upon which to test the pharmacology of both clinically and environmentally relevant marine toxins. Here, we examined the effects of the hydrophilic µ-CTx PIIIA and the lipophilic brevetoxins PbTx-2 and PbTx-3 on heterologously expressed EukCat ion channels from a marine diatom and coccolithophore. Surprisingly, none of the toxins inhibited the peak currents evoked by the two EukCats tested. The lack of homology in the outer pore elements of the channel may disrupt the binding of µ-CTx PIIIA, while major structural differences between mammalian sodium channels and the C-terminal domains of the EukCats may diminish interactions with the brevetoxins. However, all three toxins produced significant negative shifts in the voltage dependence of activation and steady state inactivation, suggesting alternative and state-dependent binding conformations that potentially lead to changes in the excitability of the phytoplankton themselves.
Insights
Marine toxins like brevetoxins and µ-conotoxins surprisingly did not inhibit novel eukaryotic protist ion channels (EukCats). However, these toxins altered channel activation and inactivation, potentially affecting phytoplankton excitability.
Area of Science:
- Marine biology
- Neuroscience
- Biochemistry
Background:
- Single-domain voltage-gated ion channels (EukCats) from eukaryotic protists are novel targets for toxin pharmacology.
- Marine toxins, including brevetoxins and µ-conotoxins, are relevant to clinical and environmental studies.
Purpose of the Study:
- To investigate the effects of specific marine toxins (µ-CTx PIIIA, PbTx-2, PbTx-3) on EukCat ion channels.
- To understand the potential interactions between these toxins and novel ion channel structures.
Main Methods:
- Heterologous expression of EukCat ion channels from marine diatom and coccolithophore.
- Electrophysiological assessment of toxin effects on channel function.
Main Results:
- No inhibition of peak currents was observed for EukCats with µ-CTx PIIIA, PbTx-2, or PbTx-3.
- All tested toxins induced significant negative shifts in the voltage dependence of activation and steady-state inactivation.
Conclusions:
- Structural differences in EukCats may explain the lack of toxin-mediated current inhibition.
- Toxins may bind to alternative conformations, altering phytoplankton excitability.
- EukCats represent a distinct class of ion channels with unique toxin interaction profiles.
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