An investigation into the mechanisms of sympathetic neuromuscular transmission.

Stimulation of the sympathetic nerves innervating the rodent vas deferens elicits excitatory junction potentials (ejps). Intermittent transient accelerations in the rising phase of these ejps, termed discrete events (d.e.s.), were observed. D.e.s. were shown to reflect packets of transmitter acting on the recording cell. They vary in latency, amplitude and time course. D.e.s. with similar latency and time course have been associated into 'families'. Families of d.e.s., generally, have multimodal amplitude distributions with clearly defined modes. Families were shown to reflect transmitter release from a single terminal nerve fibre. Variation in [Ca]o altered the relative proportion of occurrence of large and small d.e.s., in a family, without affecting the modes themselves. Facilitation had the same effect. Therefore, families of d.e.s. represent the packeted, intermittent, release of transmitter from a single release site which may be either one varicosity or a group of varicosities on a single nerve fibre. Spontaneous d.e.s. have also been observed. In most cells the amplitude distribution of spontaneous d.e.s. was unimodal and this mode was equal to the smallest evoked d.e. mode in the same cell. Transmitter release from individual release sites could be modulated by ?-adrenoreceptor agonists and antagonists. However, the effect of such drugs was not consistent with the presence of an endogenous system of modulation via prejunctional ?-receptors. No evidence could be found for endogenous inhibitory modulation of release from pulse to pulse. Rather, short term facilitation appeared to occur. Blockade of neuronal uptake of noradrenaline by desmethylimipramine had no effect on d.e.s. Higher concentrations of desmethylimipramine altered the time course of ejps and d.e.s. Finally d.e.s. were recorded in the rat tail artery. This may provide a more clinically relevant preparation for future studies.