The major interest of the investigators is in mechanisms for changing the size of the quanta of neurotransmitter that are released from the motor nerve terminal. They have found that a number of hormones roughly double the number of transmitter molecules released in each quantum, and are investigating the intracellular transduction pathways that operate to produce these hormones' effects. An interesting recent development was the demonstration that one of these signaling pathways to increase quantal size is blocked by anandamide, a naturally-occurring ligand of the cannabinoid receptor. The evidence so far suggest that some of the increase in quantal size is due to the incorporation of more transmitter into the quanta in a distinct loading stage, which occurs in those vesicles that are poised for release. There is also evidence for the continued release of some transmitter from the point on the nerve terminal at which the vesicle has fused, which adds to the size and duration of the postjunctional response. The ability to increase quantal size has significant potential for the therapy of a number of neuromuscular disease, in which transmission is depressed. They are also investigating the mechanisms by which the liberated transmitter acts back on the nerve terminal to reduce the number of quanta released by nerve stimulation. They propose to determine whether this effect is due to a depression of calcium influx into the stimulated terminal or whether the inhibition is at a later step in the release process. These studies are relevant to the action of drugs used to block neuromuscular transmission during surgery.
