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Updated: Jul 17, 2026
08:46
A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
Published on: December 2, 2022
Pyrethroid action on calcium channels: neurotoxicological implications.
J Marshall Clark1, Steven B Symington
1Department of Veterinary and Animal Science, University of Massachusetts, Morrill 1 N311, 639 N. Pleasant St., Amherst, MA 01003, USA. jclark@vasci.umass.edu
Invertebrate Neuroscience : IN
|February 13, 2007
Summary
Deltamethrin, unlike cismethrin, enhances neurotransmitter release by targeting specific calcium channels (Ca(v)2.2) in rat brains. This action depends on the channel
Area of Science:
- Neuroscience
- Toxicology
- Molecular Pharmacology
Background:
- Pyrethroids are widely used insecticides.
- Cismethrin and deltamethrin are structurally distinct pyrethroids with different toxicological profiles.
- Rat brain synaptosomes are crucial for studying neurotransmitter release.
Purpose of the Study:
- To compare the functional actions of cismethrin and deltamethrin on rat brain synaptosomes.
- To identify the specific molecular targets of deltamethrin's action.
- To elucidate the mechanism underlying deltamethrin-induced neurotransmitter release.
Main Methods:
- Functional analysis of rat brain synaptosomes.
- Electrophysiological recordings of heterologously expressed Ca(v)2.2 channels.
- Site-directed mutagenesis of the Ca(v)2.2 alpha(1)-subunit.
Main Results:
- Both pyrethroids increased calcium influx, but only deltamethrin enhanced Ca(2+)-dependent neurotransmitter release.
- Deltamethrin's action was stereospecific, concentration-dependent, and blocked by omega-conotoxin GVIA.
- Deltamethrin directly modified Ca(v)2.2 channels, with the effect dependent on the channel's phosphorylation state.
Conclusions:
- Deltamethrin specifically targets N-type Ca(v)2.2 voltage-sensitive calcium channels (VSCCs) in rat brains.
- The phosphorylation state of Ca(v)2.2 channels dictates deltamethrin's modulatory effect.
- These findings offer a potential explanation for the differing toxicological effects of cismethrin and deltamethrin.
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