Chapter 21: Storage and release of acetylcholine in a sympathetic ganglion

Abstract

This chapter discusses the behavior of releasable transmitter, if it is stored in at least two compartments: one, a readily releasable store, provides ACh immediately available for secretion and the other contains transmitter that awaits mobilization to sites of release. This idea was formulated by Birks and MacIntosh, on the basis of their kinetic analysis of the rate of ACh released from a sympathetic ganglion stimulated through its nerve trunk. Their analysis of the release of pre-formed ACh yielded a bi-exponential relationship, and they concluded that some 15% of releasable ACh was discharged with a faster time-constant than the less readily releasable store. Since this pioneering analysis by Birks and MacIntosh, a variety of evidence has been presented supporting the idea that the stored ACh in cholinergic terminals behaves as if it is heterogeneous with respect to release kinetics and to ACh turnover. Morphology of nerve terminals has shown a population of synaptic vesicles closely associated with sites of release, the active zone, whereas other vesicles clearly require mobilization to bring them to the proximity of docking sites at the active zone. Thus, the concept of transmitter mobilization from reserve to readily releasable stores of ACh has become established. But the mechanisms that regulate this process have not been well explored. This chapter presents three examples of factors that appear to interact or influence this process of mobilization.