Thesleff S
Department of Pharmacology, University of Lund, Sweden.
Fundam Clin Pharmacol. 1988;2(2):89-101. doi: 10.1111/j.1472-8206.1988.tb00625.x.
The classical studies of Katz and co-workers have shown that nerve impulses release quanta of acetylcholine at the neuromuscular junction. This release is regulated by presynaptic calcium and accounts for the trans-synaptic transmission of nerve impulses. In resting conditions it gives rise to small spontaneous potentials, i.e. miniature endplate potentials. In addition these investigators described a spontaneous molecular leakage of acetylcholine from the motor nerve. I have studied a third type of acetylcholine release. It is a spontaneous intermittent secretion of acetylcholine which postsynaptically causes large, generally slow rising potentials. This release is unaffected by presynaptic calcium and is therefore not influenced by nerve activity. The acetylcholine responsible for these potentials comes from the same pool of transmitter as that liberated by nerve impulses. The observation that the release is blocked by drugs that prevent the accumulation of acetylcholine into synaptic vesicles indicates that the secretion originates from clusters of vesicles or large vesicle-like structures in the nerve terminal. This type of release is present at a low frequency at normal neuromuscular junctions. It is markedly accelerated whenever the calcium-dependent quantal release of acetylcholine is blocked or impaired. The drug 4-aminoquinoline selectively stimulates this release. I speculate that this type of transmitter secretion is important for the development of synaptic connexions.
