Potent modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels by the type II pyrethroid deltamethrin.
J Pharmacol Exp Ther
; 284(3): 958-65, 1998 Mar.
Article
em En
| MEDLINE
| ID: mdl-9495855
ABSTRACT
In both tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) sodium channels, deltamethrin greatly prolonged the current during step depolarizing pulse and caused a large and prolonged slow tail current. The activation was shifted by 20 mV in the hyperpolarizing direction. These changes in channel kinetics account for the prolongation of action potential, membrane depolarization and spontaneous discharges in the deltamethrin-treated neurons. The slow tail current of TTX-S sodium channels rose and decayed slowly, showing a hook. By contrast, the slow tail current of TTX-R channels occurred quickly upon step repolarization. The slow tail current in deltamethrin-treated cells developed slowly during a depolarizing pulse, with a time constant in the order of several milliseconds. The percentages of sodium channels modified by deltamethrin were measured as a function of the deltamethrin concentration. The EC50 values were 0.53 microM and 0.37 microM for TTX-S and TTX-R sodium channels, respectively. However, when compared at the level of 5% modification, the potency of deltamethrin for TTX-R channels was 40 to 50 times higher than that for TTX-S channels. Deltamethrin-induced large and prolonged tail current was hardly reversed after prolonged washout with drug-free solution. However, after application of tetramethrin, it was converted into a much shorter tail current. Washout with solution devoid of tetramethrin and deltamethrin resulted in rapid reappearance of the deltamethrin-type tail current. These results suggest that the deltamethrin and tetramethrin share a binding site on the sodium channel and that the slow onset and offset of deltamethrin action are controlled by the rates at which deltamethrin moves and unbinds from the membrane lipid phase rather than by the rate of deltamethrin binding to the sodium channel site.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piretrinas
/
Tetrodotoxina
/
Canais de Sódio
/
Inseticidas
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos