Specific modulation of sodium channels in mammalian nerve by monoclonal antibodies

Monoclonal antibodies (mAbs) were generated against the sodium channels in the intact membrane of the eel electroplax. These antibodies bind to nodes of Ranvier, as indicated by immunofluorescence. When externally applied to rat nerve fibers one of these mAbs blocks impulse conduction. In voltage-clamp experiments, this mAb was found to attenuate sodium current amplitude without affecting the time course. The dose-response curve was very steep and had an ED50 of 133 nM. About half of the mAb effect was shown to be due to a shift, in the hyperpolarizing direction, of the steady-state sodium inactivation versus membrane potential curve. The remaining effect was voltage- and time-independent. This mAb had no effect on the potassium or leakage currents. The results indicate that on the external surface of the sodium channel, there are a number of antigenically similar determinants, which are functionally linked to specific elements of the sodium conductance system. These functionally related determinants were preserved through the course of evolution.