N-Ethylmaleimide modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons

The effects of N-ethylmaleimide (NEM), an alkylating reagent to protein sul fhydryl groups, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistan t (TTX-R) sodium channels in rat, dorsal root ganglion (DRG) neurons were s tudied using the whole cell configuration of patch-clamp technique. When cu rrents were evoked by step depolarizations to 0 mV from a holding potential of -80 mV NEM decreased the amplitude of TTX-S sodium current, but exerted little or no effect on that of TTX-R sodium current. The inhibitory effect of NEM on TTX-S sodium channel was mainly due to the shift of the steady-s tare inactivation curve in the hyperpolarizing direction. NEM did not affec t the voltage-dependence of the activation of TTX-S sodium channel. The ste ady-state inactivation curve for TTX-R sodium channel was shifted by NEM in the hyperpolarizing direction as that for TTX-S sodium channel. NEM caused a change in the voltage-dependence of the activation of TTX-R sodium chann el unlike TTX-S sodium channel. After NEM treatment, the amplitudes of TTX- R sodium currents at test voltages below -10 mV were increased, but those a t more positive voltages were not affected, This was explained by the shift in the conductance-voltage curve for TTX-R sodium channels in the hyperpol arizing direction after NEM treatment. (C) 2000 Elsevier Science B.V. All r ights reserved.