The heterogeneity of vesicular acetylcholine storage in cholinergic nerve terminals

The vesicular hypothesis of quantal acetylcholine release describes the process by which discrete packages (or quanta) of the transmitter are released from nerve terminals through the exocytosis of the content of synaptic vesicles. However, cholinergic synaptic vesicles can no longer be vaguely regarded as simple membrane bound 'sacks' of the transmitter. Modern molecular, biochemical, morphological and electrophysiological research has revealed them to be complex cellular structures with a heterogeneous mixture of functions. Thus, not all synaptic vesicle populations are formed under the same circumstances and there are variations in the releasability of synaptic vesicle populations. This review briefly outlines some of the experimental research that has lead to our current thinking on the heterogeneity of vesicular acetylcholine storage in cholinergic nerve terminals. In addition, a model for vesicular acetylcholine storage and release is presented that attempts to accommodate many of the modern ideas concerning cholinergic synaptic vesicle function and interaction.