Abstract
Indoxacarb is a newly developed insecticide with high insecticidal activity and low toxicity to non-target organisms. Its metabolite, DCJW, is known to block compound action potentials in insect nerves and to inhibit sodium currents in cultured insect neurons. However, little is known about the effects of these compounds on the sodium channels of mammalian neurons. We compared the effects of indoxacarb and DCJW on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons by using the whole-cell patch clamp technique. Indoxacarb and DCJW at 1-10 μM slowly and irreversibly blocked both TTX-S and TTX-R sodium channels in a voltage-dependent manner. The sodium channel activation kinetics were not significantly modified by 1 μM indoxacarb or 1 μM DCJW. The steady-state fast and slow inactivation curves were shifted in the hyperpolarization direction by 1 μM indoxacarb or 1 μM DCJW indicating a higher affinity of the inactivated sodium channels for these insecticides. These shifts resulted in an enhanced block at more depolarized potentials, thus explaining voltage-dependent block, and an apparent difference in the sensitivity of TTX-R and TTX-S channels to indoxacarb and DCJW near the resting potential. Indoxacarb and its metabolite DCJW cause toxicity through their action on the sodium channels.
Original language | English (US) |
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Pages (from-to) | 83-96 |
Number of pages | 14 |
Journal | NeuroToxicology |
Volume | 24 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2003 |
Funding
This study was supported by National Institutes of Health grant NS14143. The samples of indoxacarb and DCJW were provided by E.I. DuPont de Nemours and Company, Newark, Delaware. The authors thank Nayla Hasan for technical assistance and Julia Irizarry for secretarial assistance.
Keywords
- Dorsal root ganglion
- Indoxacarb
- Insecticide
- Sodium channel
- Sodium inactivation
ASJC Scopus subject areas
- General Neuroscience
- Toxicology