JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 17, 2007; DOI: 10.1124/jpet.107.128694

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.107.128694v1
324/1/149    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gautier, H.
Right arrow Articles by Lapied, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gautier, H.
Right arrow Articles by Lapied, B.


Received for publication July 16, 2007.
Revised October 16, 2007.
Accepted for publication October 16, 2007.

Calcium-Activated Potassium Channels in Insect Pacemaker Neurons as Unexpected Target Site for the Novel Fumigant Dimethyl Disulfide

Helene Gautier 1, Jacques Auger 2, Christian Legros 1, Bruno Lapied 1*

1 Universite d'Angers 2 Universite de Tours

* Address correspondence to: E-mail: bruno.lapied{at}univ-angers.fr

Abstract

Dimethyl disulfide (DMDS), a plant-derived insecticide, is a promising fumigant as a substitute for methyl bromide. To further understand the mode of action of DMDS, we examined its effect on cockroach octopaminergic neurosecretory cells, called dorsal unpaired median (DUM) neurons, using whole cell patch-clamp technique, calcium imaging and antisense oligonucleotide strategy. At low concentration (1 µM), DMDS modified spontaneous regular spike discharge into clear bursting activity associated with a decrease of the amplitude of the afterhyperpolarization. This effect led us to suspect alterations of calcium-activated potassium currents (IKCa) and intracellular calcium ([Ca2+]i) changes. We showed that DMDS reduced amplitudes of both peak transient and sustained components of the total potassium current. IKCa was confirmed as a target of DMDS by using iberiotoxin, cadmium chloride and pSlo antisense oligonucleotide. In addition, we showed that DMDS induced [Ca2+]i rise in Fura-2 loaded DUM neurons. Using calcium-free solution, and LOE 908 (an inhibitor of TRP{gamma}), we demonstrated that TRP{gamma} initiated calcium influx. By contrast, omega-conotoxin GVIA (an inhibitor of N-type HVA calcium channels), did not affect the DMDS-induced [Ca2+]i rise. Finally, the participation of the calcium-induced calcium release mechanism was investigated using thapsigargin, caffeine and ryanodine. Our study revealed that DMDS-induced elevation in [Ca2+]i modulated IKCa in an unexpected bell-shaped manner via intracellular calcium. In conclusion, DMDS affects multiple targets, which could be an effective way to improve pest-control efficacy of fumigation.


Key words: Dimethyl Disulfide, calcium-activated potassium channels, dorsal unpaired median neuron, fumigant, intracellular calcium, neuronal pacemaker activity




Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics.