Multiple interactions of anticholinesterases with Aplysia acetylcholine responses

The effects of the carbamate anticholinesterases neostigmine and pyridostigmine on the kinetics of densensitization of responses of isolated, voltage-clamped Aplysia neurons to microperfused acetylcholine (ACh) was examined. The peak ACh-induced current was potentiated at low carbamate doses and antagonized at higher doses (> 10 −5M); neostigmine was more potent than pyridostigmine in producing both effects. These effects suggest two mechanisms of action of these compounds: (a) inhibition of acetylcholinesterase at low doses, which increases the effective ACh dose, and (b) direct antagonism of the response at higher concentrations, which is associated with a slowing of both the activation and desensitization of the ACh response. These compounds may therefore have direct actions on the excitatory ACh receptor in Aplysia neurons which are similar to the effects of these drugs at the vertebrate endplate.