Block of two subtypes of sodium channels in cockroach neurons by indoxacarb insecticides

Indoxacarb, a novel insecticide, and its decarbomethoxyllated metabolite, DCJW, are known to block voltage-gated Na+ channels in insects and mammals, but the mechanism of block is not yet well understood. The present study was undertaken to characterize the action of indoxacarb and DCJWon cockroach Na+ channels. Na+ currents were recorded using the whole-cell patch clamp technique front neurons acutely dissociated front thoracic ganglia of the American cockroach Periplaneta americana L. Two types of tetrodotoxin-sensitive Na+ currents were observed, with different voltage dependencies of channel inactivation. Type-I Na+ currents were inactivated at more negative potentials than type-II Na+ currents. As a result, these two types of Na+ channels responded to indoxacarb compounds differentially At a holding potential of -100 mV type-I Na+ currents were inhibited reversibly by 1 mu M indoxacarb and irreversibly by 1 mu M DCJW in a voltage-dependent manner, whereas type-II Na+ currents were not affected by either of the compound. However; type-II Na+ currents were inhibited by indoxacarb or DCJW at more depolarizing membrane potentials, ranging from -60 to -40 mV. The slow inactivation of type-I and type-II Na+ channels were significantly shifted in the hyperpolarizing direction by indoxacarb and DCJW, suggesting that these compounds have high affinities for the inactivated state of the Na+ channels. It was concluded that the differential blocking actions of indoxacarb insecticides oil type-I and type-II Na+ currents resulted from their different voltage dependence of Na+ channel inactivation. The irreversible nature of DCJW block may be partially responsible for its patent action in insects. (c) 2005 Elsevier Inc. All rights reserved.