Geometry, kinetics and plasticity of release and clearance of ATP and noradrenaline as sympathetic cotransmitters: roles for the neurogenic contraction.

The paper compares the microphysiology of sympathetic neuromuscular transmission in three model preparations: the guinea-pig and mouse vas deferens and rat tail artery. The first section describes the quantal release of ATP and noradrenaline from individual sites. The data are proposed to support a string model in which: (i) most sites (> or = 99%) ignore the nerve impulse and a few (< or = 1%) release a single quantum of ATP and noradrenaline; (ii) the probability of monoquantal release is extremely non-uniform; (iii) high probability varicosities form 'active' strings; and (iv) an impulse train causes repeated quantal release from these sites. Analogy with molecular mechanisms regulating transmitter exocytosis in other systems is proposed to imply that coincidence of at least two factors at the active zone, Ca2+ and specific cytosolic protein(s), may be required to remove a 'fusion clamp', form a 'fusion complex' and trigger exocytosis of a sympathetic transmitter quantum, and that the availability of these proteins may regulate the release probability. The second section shows that clearance of noradrenaline in rat tail artery is basically > or = 30-fold slower than of co-released ATP, and that saturation of local reuptake and binding to local buffering sites maintain the noradrenaline concentration at the receptors, in spite of a profound decline in per pulse release during high frequency trains. The third section describes differences in the strategies by which mouse vas deferens and rat tail artery use ATP and noradrenaline to trigger and maintain the neurogenic contraction.