Autonomic neuromuscular transmission at a varicosity

This review attempts to clarify the definition of what constitutes an autonomic neuromuscular function formed by a varicosity. Ultrastructural studies of serial sections through varicosities, partly or wholly bare of Schwann cell covering, show that areas of close apposition occur between varicosities and muscle cell membrane that vary between 20 and 150 nm, depending on the muscle considered. Consideration of the diffusion of purine transmitters and their receptor kinetics after secretion in a packet show that the number of purinergic receptor channels opened at a site of 150 nm apposition by a varicosity is about 15% of that at a site of 50 nm apposition. These results, together with the analysis of the stochastic fast component and the deterministic slow components of the rising phase of the EJP suggest that the stochastic fast component is due to varicosities that form especially close appositions (20-50 nm), whereas the deterministic slow component is due to the large number of varicosities at distances up to about 150 nm. Varicosities forming appositions of 20-150 nm with muscle cells several hundred micrometers long possess junctional receptor types distinct from extrajunctional receptors. According to this argument, then, there are two different classes of varicosities: one that gives rise to a relatively large junctional current and another that is responsible for a very small junctional current. Present evidence suggests that two subclasses of varicosities can be discerned amongst the varicosities that generate large junctional currents. One of these subclasses of varicosity possesses relatively few post-junctional receptors compared with the amount of transmitter reaching the receptors from the varicosity, so that the junctional current generated is determined by the size of the receptor population; in this case, the size of the transmitter packages released from these varicosities is unknown and the size of the junctional current is relatively constant. The other subclass of varicosity possesses large receptor patches, sufficient to accommodate the largest amounts of transmitter released from the varicosities: in this case, the size of the transmitter packages is shown to be highly non-uniform. These speculations await confirmation by direct labelling of the receptor patches beneath varicosities, a possibility that is likely to be realized in the near future.