The research program of our laboratory involves four areas: 1. Receptor Desensitization. The research provides experimental results and data to be used in the formulation of a more complete kinetic model of receptor desensitization. The experiments are also designed to provide means for distinguishing between molecular mechanisms proposed to explain desensitization. The work is carried out on frog nerve-muscle preparations in vitro. Factors which contribute to the susceptibility and resistance to desensitization by cholinergic agonists and other agents are under study. 2. Amphibian Model of Myasthenia Gravis. This investigation involves characterization and utilization of an amphibian model for myasthenia gravis newly discovered in our laboratory. The electrophysiological and ultrastructural changes in these frogs which have been immunized against cholinergic receptor protein are studied in vivo and in vitro using nerve muscle preparations. The neuromuscular block produced is characterized by reduction in postjunctional response to carbamylcholine, low amplitude miniature endplate potentials, and subcritical endplate potentials. 3. Effects of delta 9-tetrahydrocannabinol (delta 9-THC) on Cholinergic Transmission. This study involves exploration of possible sites and modes of action of delta 9-THC at various pre and post synaptic loci using standard single fiber techniques. The possible influence of delta 9-THC on cholinergic receptor desensitization is also to be explored. 4. Synaptic Vesicle Cycle at the neuromuscular junction. Preliminary studies have shown that intense depolarization using K ion propionate causes massive discharge of synaptic vesicles from motor nerve terminals. Structural alterations include formation of large cisternae which communicate with the synaptic cleft, coated vesicles, and coated pits. These changes are reversed and neuromuscular transmission recovers when the preparation is returned to normal Ringer solution.