QUANTAL ACETYLCHOLINE-RELEASE AT THE VERTEBRATE NEUROMUSCULAR-JUNCTION

The ACh that is released to transmit the signal from nerve to muscle is packaged in vesicles and consequently is released as quanta. Quantal release enables the synapse to work fast. The released ACh diffuses through a meshwork of AChE, which is one of the fastest enzymes known. The enzyme in the diffusion path is saturated by the high local concentration of ACh, so plenty of the ACh reaches the end plate. The high concentration at the end plate opens many ACh receptor channels almost synchronously. The receptors release the bound ACh and close rapidly, but because the release is asynchronous, almost all that comes off is promptly destroyed by the enzyme. We do not find the evidence that quanta are made up of subunits persuasive. The difference between the rate of spontaneous quantal release and the maximum evoked release is about the same as the difference between the rate of a spontaneous chemical transformation and the rate when it is enzymatically catalyzed. Viewed in this light, spontaneous release does not seem so exceptional, nor does it necessarily serve a signaling function. What is notable compared with most chemical reactions is that we can so readily detect the individual events. Our overall conclusion is that there still is much to do. From the standpoint of the pioneers at the NMJ, we have made almost unimaginable progress, now sorting out the molecules that make up the exocytotic apparatus. Many fundamental questions remain unanswered however. We do not understand seemingly simple plastic changes, such as facilitation or depression. We have only the vaguest concepts of how the vesicles are formed, transported to the active zones, and released. We know that Ca2+ plays a central role in regulating release, but the site(s) at which it acts remains unknown. We could extend this list, but the point is that the NMJ is an accessible synapse, unmatched for measuring quantal release, that still has much to teach us.