The physiological role of three acetylcholine receptors in synaptic transmission in Aplysia.

1. It is shown that a single presumably cholinergic presynaptic neurone can mediate, monosynaptically, multicomponent responses in a given cell and different responses in different cells.2. Complex responses (whether evoked synaptically or by ACh injection) are shown to be the result of the coexistence on a given post-synaptic neurone of more than one of three cholinergic receptor types previously described. Likewise, different responses in different cells are due to the fact that different post-synaptic neurones bear different combinations of these three receptors.3. Pharmacological analysis shows that the multicomponent nature of many of the responses is not always evident: what appears, under normal conditions, to be a single-component excitatory potential can be shown often to be a complex response consisting of superimposed e.p.s.p.s and rapid i.p.s.p.s which are sometimes, though not always, accompanied by a slow i.p.s.p.4. Although which and how many of the three receptor types is the major factor contributing to the type of response observed, in the case of some of the synaptic potentials certain other factors were found to contribute to the final response form. First, in the large cells of the visceral ganglion, as well as in the left giant cell of the pleural ganglion, there is a marked ;electrical separation' between the region in which the synaptic currents are generated and the point of recording. This ;electrical distance' often altered the inversion potential, and sometimes the form of the responses. Secondly, in some visceral neurones, activation of the cholinergic presynaptic neurone L10 causes (either directly or indirectly) a potential change which cannot be accounted for in terms of the activation of cholinergic receptors. This ;non-cholinergic' response (not imitated by an ionophoretic injection of ACh) is unmasked by the blocking of all three cholinergic receptors. It contributes differentially in different cells to the total response pattern produced by L10 under normal conditions, but its contribution is often characterized by a late hyperpolarizing phase which appears to be impossible to invert. This phase has been shown, however, to be dependent upon the potassium concentration in the extracellular space surrounding the synapse.4. It is tentatively suggested that this residual, non-cholinergic element of the synaptic response in some visceral cells be the result of the activation of an electrical synapse.