This account deals with studies of slow synaptic potentials, a new peptidergic transmitter, and integrative mechanisms at synapses in vertebrate autonomic ganglia.
In neurones of the cardiac parasympathetic ganglia of the mudpuppy (Necturus maculosus) both rapid excitatory and slow inhibitory synaptic potentials interact. The same transmitter, acetylcholine (ACh), causes in individual neurones a fast e.p.s.p. lasting up to 50 ms and a slow i.p.s.p. of about 2 s. The sequence of processes leading to these two synaptic potentials differs in important respects. Molecules of ACh released by terminals of the vagus combine with nicotinic receptors and within a fraction of 1 ms initiate the rapid e.p.s.p. which, as a rule, leads to a conducted impulse in ganglion cells. The e.p.s.p. resembles in its ionic mechanisms the rapid excitatory synaptic events seen at most neuromuscular and neuronal synapses. ACh also combines with muscarinic receptors whose activation is followed by an increased flow of K+ ions and the generation of a slow i.p.s.p. There occurs, however, an apparent delay of over 100 ms between the time ACh reaches the muscarinic receptors and the detectable activation of the inhibitory conductance. During the delay the nicotinic e.p.s.p. has declined and ACh has disappeared from the synaptic cleft. It is suggested that at least three distinct processes are involved in the activation of the inhibitory conductances.
The second part of this paper describes synaptic events in sympathetic ganglia of the frog where release of ACh initiates three different synaptic potentials: (i) a standard fast nicotinic e.p.s.p. (about 30-50 ms duration); (ii) a slow muscarinic e.p.s.p. (30–60 s); (iii) a slow i.p.s.p. (about 2 s). The fourth synaptic signal, the ‘late slow e.p.s.p.’, lasts 5–10 min and is not caused by ACh.
We have evidence that a peptide, resembling luteinizing hormone releasing hormone (LHRH), is secreted by specific axons within ganglia where it initiates the late slow e.p.s.p.s. The evidence for such a peptidergic transmitter is as follows: (1) In nerves whose stimulation leads to the late slow e.p.s.p.s one detects by radioimmunoassay a peptide with a molecular weight of about 1000 daltons, resembling LHRH. (2) The peptide is released in isotonic KCl if Ca2+ is present in the high K+ solution. (3) Five days after cutting the appropriate presynaptic nerves, about 95% of the peptide disappears from the ganglia. At the same time the content of peptide central to the cut is increased, suggesting that it is concentrated in axons and transported to the periphery from the spinal cord. (4) Application of synthetic LHRH mimics the action of the nerve-released transmitter in a specific manner. Both substances cause similar changes in the postsynaptic membrane conductance and in the excitability of neurones, and the depolarizing effect of both agents changes in parallel when neurones are hyperpolarized. (5) An analogue of LHRH which in mammals blocks the release of gonadotropins also blocks the depolarizing effect of nerve-released transmitter and of applied LHRH in ganglion cells. Similar parallel actions occur after the application of other analogues of LHRH, some of which are more potent agonists, and others which are not effective. It is suggested that the natural transmitter and LHRH and its analogues act on the same receptors.
The role of slow synaptic potentials and the way in which they influence the effectiveness of cholinergic stimulation are discussed. Since the various synaptic potentials interact in individual cells, these neurones are suitable for a study of integrative mechanisms.