Utilization of Superfused Cerebral Slices in Probing Muscarinic Receptor Autoregulation of Acetylcholine Release

Signal transmission from cholinergic nerves is mediated by two classes of receptors: (1) ionotropic nicotinic receptor channels and (2) metabotropic (G-protein coupled) muscarinic receptors. The muscarinic receptor family comprises five receptor subtypes (M1 through M5), each encoded by its gene. Individual subtypes exert important and specific roles in various physiological processes, ranging from vegetative to cognitive functions and memory. Cloning of individual muscarinic receptor subtypes has enabled targeted studies of ligand binding and activation characteristics of the recombinant protein and a rapid increase in the development of receptor-selective drugs for various potential therapeutic uses. Results of testing new drugs obtained on recombinant proteins need to be verified using systems that better mimic a physiological environment. Here we provide a brief outline and examples of the utilization of superfused brain slices for probing drug effects on muscarinic autoreceptor-mediated regulation of acetylcholine release.