Release of acetylcholine in the isolated heart

Abstract

This article summarizes methods for studying release of acetylcholine (ACh) in the heart and reviews the literature on release, synthesis, and inactivation of ACh. Cholinergic mechanisms involved in cardiac neuroeffector transmission are, in principle, the same as in ganglia and motor endplates, but their relative functional significance exhibits unique features. First, release of ACh evoked by nerve stimulation is maintained at a high level due to rapid formation of free extracellular choline from phospholipids. Choline derived from ACh hydrolysis plays a minor role in ACh synthesis. The constant efflux of choline allows continuous monitoring of changes in formation and removal of extracellular choline, e.g., by activation of neuronal uptake during nerve stimulation. Second, ACh released from terminal nerve fibers is rapidly washed into the circulation and thereby escapes hydrolysis by cholinesterase activity to a functionally significant extent. Hydrolysis and diffusion appear as equally important mechanisms of transmitter inactivation in the heart. The cardiac neuroeffector junction is not a morphological or functional entity restricted to adjacent pre- and postsynaptic elements.