ATP as a sympathetic co-transmitter in rat vasomotor nerves--further evidence that individual release sites respond to nerve impulses by intermittent release of single quanta.

A combination of intra- and extracellular recording was used to study neurotransmitter release in sympathetic vasomotor fibres in rat femoral and mesenteric arteries. The results show that neurotransmission in these preparations is similar to that in the 'short' sympathetic nerves in guinea-pig vas deferens and the 'long' sympathetic nerves in rat tail artery in the following respects: (1) The intracellularly recorded excitatory junction potentials (EJPs) and the extracellularly recorded junction currents (EJCs) presumably are caused by ATP secreted as a sympathetic co-transmitter. (2) The stimulus-evoked and spontaneous EJCs share the same brief time-course, which is similar to that of spontaneous EJPs, but much briefer than that of stimulus-evoked EJPs. (3) 'Successful' nerve impulses appear to release single transmitter quanta. (4) The probability of activation of individual release sites is low (0.002-0.02). (5) The low release probability cannot be accounted for by failure of the nerve impulse to invade the terminals. Moreover, it is also shown that application of tetrodotoxin to the medium within the recording electrode effectively abolishes transmitter secretion in the area enclosed by the tip of the electrode, indicating that the effective length constant for a passively propagating nerve action potential is probably very small and that activation of the release mechanisms in 'long' sympathetic nerve fibres seems to require that the varicosities are actively invaded.