A monoclonal immunotoxin acting on the Na+ channel, with properties similar to those of a scorpion toxin

Abstract

We describe the properties of a monoclonal antibody against the Na+ channel. The antibody, 72.38, competitively inhibited (Ki = 1.5 X 10(-9) M) the binding of an 125I-labeled toxin from the Brazilian scorpion Tityus serrulatus (125I-TiTX gamma) to Na+ channels of rat brain membranes. No significant inhibition of binding of a number of other Na+ channel toxins was observed. The inhibition of 125I-TiTX gamma binding also was observed with the solubilized Na+ channel from rat brain membranes (Ki = 2 X 10(-9) M). Antibody 72.38 antagonized 125I-TiTX gamma binding to Na+ channels from different animal species (fish, avian, and mammalian) and from different tissues (electroplax, brain, heart, and muscle). Moreover, 72.38 has been used for immunofluorescence labeling of Na+ channels in rat sciatic nodes of Ranvier and cultured dorsal root ganglion cells. Electrophysiological experiments on rat muscle cells fully confirmed the similarity between TiTX gamma and 72.38 seen in binding experiments. Both produce slow oscillations of the membrane potential accompanied by bursts of action potentials which are due to a selective action on the Na+ channel. TiTX gamma and 72.38 are without effect on the ion selectivity of the Na+ channel, but they both drastically change the voltage-dependence of activation and inactivation of the Na+ channel.