Acetylcholine (ACh) is the neurotransmitter that allows nerves to stimulate skeletal muscles to contract. The muscle receptors that accept this ACh message are well described, and many compounds (referred to as cholinergic drugs) are known to act on these muscle ACh receptors. These same cholinergic drugs seem to affect the nerves that innervate these muscles. The drugs can affect the ability of the nerve to become excited (and generate action potentials), as well as affect the amount of ACh that can be released by the nerves. Due to technical complexities, these drug actions on nerves have received much less attention than their affects on muscles. This project will study the actions of cholinergic drugs on the ability of nerves to become excited and to release ACh. Additionally, the nerve effects of these compounds will be compared to their muscle effects in order to see whether the nerve and muscle effects are related. One hypothesis is that an acetylcholine receptor exists on nerves as well as on muscles. This project will examine whether cholinergic drug effects on nerves are consistent with actions at these putative neuronal ACh receptors. The project will provide new information concerning cholinergic drug actions on motor nerves, and relate these actions to those on muscle endplates. Additionally, the investigations address a fundamental issue of neuromuscular transmission, role, if any, of motor nerve receptors for acetylcholine.
