Interactions of pyrethroids with the voltage-gated sodium channel.

Resumen Interacciones de los piretroides con el canalde sodio controlado por tension electrica Un modelo homologado de la region delporo del canal de sodio controlado portension electrica de la mosca domesticafue desarrollado, basado en la estructuradel canal de sodio Kv1.2, y utilizado parapredecir un punto de ligamiento para pi-retroides y DDT. Algunas prediccionesderivadas del modelo fueron validadasexperimentalmente. El modelo permitedeterminar algunos de los factores cen-trales del mecanismo de accion de los piretroides:1. El punto de ligamiento esta localizadoen una bolsa hidrofobica delimitadapor la ligadura IIS4-S5 y las helicesIIS5/IIIS6, accesible por los lipidos dedoble capa y para los insecticidas li-pido-solubles.2. El punto de ligamiento se forma du-rante la activacion (apertura) del canalde sodio y es consistente con observa-ciones de que los piretroides ligan pre-ferencialmente a canales abiertos.3. Se asume que el ligamiento de pire-troides estabiliza el estado de aperturadel canal. Esto podria tambien expli-car las senales electricas que se obser-varon despues de la repolarizacion 6. Das Modell identifiziert Schlusselstel-len in den Helices des Kv 1.2-Na-trium-Kanals, die wahrscheinlich zurdiese Substanzen beitragen.

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