Molecular Pharmacology, Vol 20, 356-362, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Voltage-Sensitive Sodium Channels in Neuroblastoma Cells by Antiarrhythmic Drugs

¹ Department of Pharmacology, University of Washington, Seattle, Washington 98195

The antiarrhythmic drugs lidocaine, quinidine, procainamide, and diphenylhydantoin block neurotoxin-activated sodium channels in neuroblastoma cells. At concentrations which effectively block sodium channels, these drugs have no effect on binding of [³H]saxitoxin to its receptor site on sodium channels. Similarly, effective concentrations of lidocaine, quinidine, and diphenylhydantoin have no effect on specific binding of ¹²⁵I-labeled scorpion toxin to sodium channels. These results show that antiarrhythmic drugs do not occupy neurotoxin receptor site 1, the tetrodotoxin/saxitoxin receptor site, or neurotoxin receptor site 3, the scorpion toxin/sea anemone toxin receptor site, in inhibiting sodium channels. The antiarrhythmic drugs are competitive inhibitors of activation of sodium channels by the full agonist batrachotoxin, but are mixed inhibitors affecting both K_0.5 and V_max for activation by the partial agonist veratridine. These results are consistent with the conclusion that the antiarrhythmic drugs are allosteric competitive inhibitors of sodium channel activation by batrachotoxin and veratridine. It is likely that antiarrhythmic drugs act at site(s) distinct from neurotoxin receptor Site 2 and alter veratridine and bactrachotoxin action indirectly.

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ACKNOWLEDGMENTS I thank Ms. Sherry Pesheck and Ms. Cynthia Morrow for excellent technical assistance.

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