Acetylcholine changes underlying transmission of a single nerve impulse in the presence of 4‐aminopyridine in Torpedo

Abstract

SUMMARY1. Transmission of a single nerve impulse has been investigated at the nerveelectroplaque junction of Torpedo marmorata in the presence of 4-aminopyridine (4-AP), a drug which powerfully potentiates evoked transmitter release.2. Three methodological approaches were used conjointly. These were (i) electrophysiological recording of the compound electroplaque potential (e.p.p.), (ii) radiochemical measurement of evoked acetylcholine (ACh) release and (iii) analysis of the content of ACh and ATP in the tissue at brief time intervals during the course of the e.p.p. and soon after. The last was achieved by using a stimulator coupled to a rapid tissue freezer.3. In the response to a single stimulus, 4-AP enhanced in a dose-dependent manner the size of the e.p.p., increasing the duration much more than the amplitude. At

Acetylcholine measured at short time intervals during transmission of nerve impulses in the electric organ of Torpedo

“…A further important remark is that the successive e.p.p.s during the 100 Hz burst did not show, either in amplitude or shape, a pattern resembling the changes in total ACh. This was also reported for oscillations of 5 s period (Dunant et al 1977), but appears not to be the case for stimulation in the presence of 4-aminopyridine where, as shown in the following paper (Corthay et al 1982), a late increase in ACh is associated with an increase in transmitter release. In the normal synapse, therefore, the amount of ACh released by a given impulse is, at least under physiological conditions, independent of the size of the intraterminal transmitter store.…”

“…Identification of bound ACh as the ACh contained in synaptic vesicles was verified in this series of experiments, using pieces of tissue frozen with our apparatus. Radioactive precursors have also been used to show that ACh is not rapidly transferred from cytoplasm to vesicles within the ms or the s time range (see Corthay et al 1982). We are therefore left with the conclusion that transmission of a brief burst of impulses in the electric organ of Torpedo is linked to important changes in the tissue ACh level, but these changes take place in the extravesicular pool of transmitter, almost certainly cytoplasmic ACh.…”

“…Stimulation consisted of a short train of impulses at a high frequency, a pattern which resembles the natural discharge of the fish in the sea. A subsequent paper (Corthay, Dunant & Loctin, 1982) will describe the ACh changes occurring during the course of a single e.p.p. in which ACh release is greatly potentiated by 4-aminopyridine.…”

Facilitation by 3,4‐diaminopyridine of regenerative acetylcholine release from mouse motor nerve

“…In the vertebrate neuromuscular junction (Lundh, 1978;Katz & Miledi, 1979;Molgo et al, 1980) and the Torpedo electric organ (Corthay et al, 1982;Muller, 1986), aminopyridines markedly potentiate and prolong the release of acetylcholine (ACh) evoked either by a focal electrical depolarization of nerve terminals or by field stimulation. Histological experiments reveal that transmissions of nerve impulses in the presence of aminopyridines are accompanied by the occurrence of endoexocytotic images in the presynaptic membrane (Heuser et al, 1979) or by the appearance of large presynaptic intramembrane particles (Garcia-Segura et al, 1986).…”

Effects of 4-aminopyridine on the non-adrenergic inhibitory neurotransmission in the guinea-pig duodenum.

“…1978; BOSTOCK et al, 1981;BURLEY and JACOBS, 1981;CORTHAY et al, 1982;THOMSEN and WILSON, 1983), 3,4-diaminopyridine (3,4-DAP) (DURANT and MARSHALL, 1980;GLOVER, 1980;MOLGO et al, 1980, THOMSEN andWILSON, 1983), and 4-methyl-2-aminopyridine (4M-2-AP) (KILOH et al, 1981). The release of adrenergic neurotransmitter was also increased by 4-AP (KIRPEKAR et al, 1977) and 4M-2-AP (GLOVER, 1980).…”