Spatiotemporal pattern of quantal release of ATP and noradrenaline from sympathetic nerves: consequences for neuromuscular transmission.

The recent explosive development in research concerning the fundamental mechanisms of synaptic transmission helps put the present paper in context. It is now evident that not all transmitter vesicles in a nerve terminal, not even all those docked at its active zones, are immediately available for release (36). We watch, fascinated, the unraveling of the amazingly complex cellular mechanisms and molecular machinery that determine whether or not a vesicle is "exocytosis-competent" (77,78,39,79). Studies on quantal release in different systems show that neurons are fundamentally similar in one respect: that transmitter release from individual active zones is monoquantal (2). But they also show that active zones in different neurons differ drastically in the probability of monoquantal release and in the number of quanta immediately available for release (3). This implies that one should not extrapolate directly from transmitter release in one set of presynaptic terminals (e.g., in neuromuscular endplate or squid giant synapse) to that in other nerve terminals, especially if they have a very different morphology. As shown here, one should not even extrapolate from transmitter release in sympathetic nerves in one tissue (e.g., rat tail artery) to that in other tissues or species (e.g., mouse vas deferens). It is noteworthy that most studies of quantal release are based on electrophysiological analysis and therefore deal with release of fast, ionotropic transmitters from small synaptic vesicles at the active zones, especially in neurons in which these events may be examined with high resolution (49,48,46,33,32). Such data are useful as general models of the release of both fast and slow transmitters from small synaptic vesicles at active zones in other systems, provided that these transmitters are released in parallel, as are apparently ATP and NA in sympathetic nerves. They tell us little or nothing, however, about the release of transmitters (e.g., neuropeptides) from the large vesicles, nor about the spatiotemporal pattern of monoquantal release from small synaptic vesicles in the many neurons that have boutons-en-passent terminals. They show that the time course of effector responses to fast, rapidly inactivated transmitters such as ACh or ATP is necessarily release related. But they do not even address the possibility that the effector responses to slow transmitters such as NA, co-released from the same terminals, may obey completely different rules and perhaps rather be clearance related (7).(ABSTRACT TRUNCATED AT 400 WORDS)