The topographical basis and frequency-dependence in the effect of different compounds on neurogenic contractions of the guinea-pig ileum.

The site of action of compounds affecting either Na+/K+ or Ca2+ conductances in nerve terminals was studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes, dividing a strip into three segments. Neurogenic stimulation of the oral segment, set up nerve action potentials in the neurons projecting axons up to the aboral segment. These axons, turning into varicose nerve terminals, conducted action potentials aborally across the middle segment (10 mm). Finally, the nerve terminals, extending into the aboral segment, might be also invaded and trigger aboral twitches. Compounds were added, either to the oral segment, to affect the genesis and spread of action potentials in the proximal parts of cholinergic neurons (cell bodies): or they were added to the middle segment to affect propagation of action potentials in axon preterminals and the proximal parts of varicose nerve terminals; or they were added to the aboral segment to affect the propagation in the endings of varicose nerve terminals. As a result, the amplitude of aboral twitches reflected drug effects at each site quantitatively. Interference with Na+/K+ conductance by an elevation of K+ concentration or by cisapride or neuropeptide Y at non-aboral segments modulated the amplitude of aboral twitches evoked by low-frequency stimulation but did not affect post-tetanic potentiation of twitches; on the other hand, changes in Ca2+ concentration of compounds affecting excitatory amino acids receptor system or omega-Conotoxin, when applied to the aboral segment, affected post-tetanic potentiation. Thus the effects of cisapride and neuropeptide Y (NPY) during low-frequency stimulation could be located to axon preterminals or the proximal parts of the terminals and their polarization. On the other hand, a new role for glutamatergic system in post-tetanic potentiation was bound to the endings of varicose nerve terminals with Ca-sensitive component in conduction.