NEURONALLY RELEASED AND APPLIED ACETYLCHOLINE ON THE LONGITUDINAL MUSCLE OF THE GUINEA-PIG ILEUM

Brief transmural stimuli, which selectively excited cholinergic fibres , initiated contractions and excitatory junction potentials in prepara tions of longitudinal muscle isolated from the guinea-pig ileum: these responses were associated with an increase in the internal concentrat ion of calcium ions. When muscle voltage-dependent calcium channels we re blocked using the organic calcium antagonist nifedipine, brief stim uli continued to initiate contractions, evoke excitatory junction pote ntials and cause an increase in the intracellular calcium concentratio n. Ionophoretically applied acetylcholine caused depolarizations which resembled the excitatory junction potentials evoked by cholinergic ne rve stimulation. Both responses had slow time courses and were abolish ed by muscarinic receptor antagonists. However, the depolarizations pr oduced by ionophoretically applied acetylcholine, unlike those produce d by nerve stimulation, were frequently interrupted by transient hyper polarizations. The transient hyperpolarizations were abolished by bari um ions or charybdotoxin. High concentrations of the calcium antagonis ts nicardipine, verapamil or diltiazem had a tendency to preferentiall y abolish the excitatory junction potential. When the effects of the c holinesterase inhibitor, eserine, on excitatory junction potentials we re examined, it became apparent that when the destruction of acetylcho line was prevented it initiated an additional conductance change to th at initiated by acetylcholine in untreated tissues. The results are di scussed in relation to the idea that neuronally released acetylcholine and applied acetylcholine might activate different subsets of muscari nic receptors on longitudinal ileal smooth muscle.