Modulation of transmitter synthesis and release in cholinergic terminals
Vaca, K.; Johnson, D.; Pilar, G.
Journal de Physiologie 78(4): 385-391
1982
ISSN/ISBN: 0021-7948 PMID: 6133949 Document Number: 185939
Ciliary nerve terminals of the iris and oculomotor nerve terminals of the ciliary ganglion in the chick were used to characterize the regulation of acetylcholine [ACh] synthesis and release. Externally provided choline is accumulated mostly by a high affinity, Na-coupled transport system and acetylated. Electrical stimulation accelerates choline uptake and acetylation by a Ca-dependent mechanism. Steady-state depolarization decreases the rates of uptake and acetylation, but each is greatly enhanced after the depolarization. Electrical stimulation and depolarizing agents release radiolabeled ACh with 1st order kinetics, the rate constant increasing with the amount of CA that enters the nerve terminal. The nerve ending more gradually mobilizes a performed store of reserve transmitter into the readily releasable pool to help sustain ACH release during high levels of activity. Intracellular recordings from presynaptic nerve terminals of the ciliary ganglion show that transient application of the cholinergic agonists, ACh and carbachol, increases the membrane conductance, thereby depolarizing the nerve ending. This effect on the nerve terminal can be blocked by the muscarinic antagonist, atropine. Both ACh and carbachol induce rapid fluctations in the membrane potential of the presynaptic terminal, suggestive of ACH receptor noise. Ca-dependent ACH release elicited by electrical stimulation or high [K+]0 [extracellular K+] depolarization is elevated above control level in the presence of atropine, suggesting that under normal conditions activation of presynaptic cholinergic receptors limits transmitter release. At early stages of transmission following synaptogenesis, there is little apparent specialization in the presynaptic membrane nor any well-defined organization of intraterminal organelles. Embryonic neuromuscular transmission fatigues very rapidly during repetitive stimulation due to an apparent decline in transmitter output at frequencies easily sustained in the adult. The fatigability is well correlated with deficiency in the regulatory processes described above such that the embryonic terminals do not accelerate transmitter synthesis in response to stimulation. Modulation of transmitter synthesis and release has an important role in maintaining normal physiology and may be intimately related to the structural organization of the nerve terminal.