Cholinergic receptors at sympathetic preganglionic nerve terminals

I The isolated hemisected frog spinal cord has been used to study the action of acetylcholine antagonists on amino acid responses by means of sucrose gap recording. 2 Primary afferents and motoneurones were shown to contain few, if any, cholinoceptors, since acetylcholine and carbachol responses were essentially abolished when synaptic transmission was blocked with magnesium ions or when action potentials were blocked by tetrodotoxin.3 Curare antagonized the y-aminobutyric acid (GABA) and ,B-alanine depolarizations of primary afferents and the hyperpolarizing action of these amino acids on motoneurones. Nicotine also antagonized 3-alanine depolarizations and to a small extent GABA depolarizations of primary afferents. These actions are similar to but weaker than those obtained previously with picrotoxin. 4 Atropine selectively antagonized 3-alanine depolarizations of primary afferents and blocked ,B-alanine and glycine hyperpolarizations of motoneurones. GABA responses were entirely resistant to the action of atropine. These actions are similar to but 50 times weaker than those obtained previously with strychnine. 5 Dihydro-,B-erythroidine, tetraethylammonium, and gallamine were entirely ineffective in antagonizing amino acid responses. Since these agents are known to block the dorsal root potential elicited by ventral root stimulation but have no effect on the amino acid responses of primary afferents, it is evident that a cholinergic step is involved in this pathway.

Section: Discussionmentioning

confidence: 99%

THE ACTION OF ACETYLCHOLINE ANTAGONISTS ON AMINO ACID RESPONSES IN THE FROG SPINAL CORD in vitro

NICOLL

1975

“…If the rat superior cervical ganglion is arranged in the sucrose-gap so that the recorded potential differences arise between the proximal pole of the ganglion and the cervical sympathetic trunk, depolarizations induced on superfusion with ACh are thought to arise mainly in the preganglionic nerve terminals (Koketsu & Nishi, 1968). This experimental arrangement is shown diagrammatically in Figure 8.…”

Section: Possible Presynaptic Actions Of S-htmentioning

confidence: 99%

Membrane Potential Changes Induced by 5‐hydroxytryptamine in the Rabbit Superior Cervical Ganglion

Wallis¹,

Woodward²

1975

I Changes in resting membrane potential induced by 5-hydroxytryptamine (5-HT) have been measured in the excised ganglion by the sucrose-gap technique. 2 5-HT produced a rapid depolarization, the threshold concentration for depolarization being around 10 MM. With concentrations of 100 MM or greater, repolarization began during the course of the superfusion; this was followed by prolonged tachyphylaxis. 3 Tachyphylaxis was largely avoided by making injections into the superfusion stream.Standard injections of 0.2 gmol 5-HT dissolved in 0.2 ml of Krebs solution were used routinely and could be given at 20-30 min intervals to evoke relatively constant responses. 4 The response to an injection consisted of a rapid depolarization, followed by a rapid repolarization and subsequent after-hyperpolarization. The threshold quantity for depolarization was around 0.01 ,umol, while the ED,, estimated from 6 dose-response curves was 0.12 ± 0.02 Mmol (mean ± s.e. mean). 5Injections of 5-HT (0.2,mol), choline (10 Mmol) and acetylcholine (9.9 ,mol) produced depolarizations of similar magnitude. 6 Monoamine oxidase inhibitors failed to alter substantially the amplitude of depolarizations to 5-HT. 7 5-HT depolarizations were unaltered in amplitude when the impermeant anion benzenesulphonate was substituted for the chloride ion in Krebs solution, but were initially markedly reduced in amplitude in a sodium-deficient medium; some recovery of the response subsequently occurred. The depolarization which persisted in sodium-deficient solutions was much reduced or abolished when calcium ions were then removed from the superfusion medium. Removal of either calcium ions alone or potassium ions from the superfusion fluid did not reduce depolarization amplitude. 8 The after-hyperpolarization was abolished in sodium-deficient solutions, usually increased in potassium-free solutions, reduced or abolished by ouabain or nicotine, but unaffected by calcium-free solutions. 9 A depolarizing action of 5-HT on presynaptic terminals in the ganglion appears probable.

“…It is now well established that ACh and ACh-like agents initiate antidromicallypropagated discharges in certain nerve terminals (for example Masland & Wigton, 1940;Feng & Li, 1941;Riker, Roberts, Standaert & Fujimori, 1957;Randic & Straughan, 1964), and that ACh can depolarize non-myelinated nerve fibres (Armett & Ritchie, 1960) including preganglionic sympathetic nerve terminals (Koketsu & Nishi, 1968). Koelle (1961Koelle ( , 1962 suggested that the presynaptic effect of ACh is an integral part of the physiology of synaptic transmission.…”

Section: Discussionmentioning

confidence: 99%

The release of acetylcholine by acetylcholine in the cat's superior cervical ganglion

Collier¹,

Katz²

1970

Summary1 The experiments described in this paper tested the effect of acetylcholine (ACh), carbachol or preganglionic nerve stimulation on the release of ACh from the cat's perfused superior cervical ganglion; radioactive tracer methods were used. 2. When the ganglion's transmitter store of ACh had been labelled, radioactive ACh was released by nerve stimulation (5 Hz for 2 min), but there was no release by ACh (015-15 jg) or by carbachol (1-10 Mig) when these drugs were injected close to the ganglion. Perfusion with low or moderate concentrations of ACh (0-15-5 jug/ml) also failed to release ACh, but high concentrations (15-50 ,tg/ml) released a small amount of labelled material. There was no correlation between ganglion stimulation by ACh and release of radioactivity.3. Ganglion-blocking concentrations of ACh did not reduce the release of ACh during continuous nerve stimulation. 4. When resting (unstimulated) ganglia were perfused with 3H-choline and eserine, the extra ACh synthesized and stored by such ganglia (surplus ACh) was labelled. Preganglionic nerve stimulation (5 Hz for 2 min) did not release surplus ACh, but perfusion with ACh (05-15 pig/ml), or injection of carbachol (0O5-2-5 ytg) did. 5. Surplus ACh released by ACh or by carbachol did not contribute to the ganglion stimulating effect of either drug. 6. It is concluded that the presynaptic effects of ACh are not of physiological importance. IntroductionThe concept that the arrival of an action potential in a presynaptic nerve terminal results in the release of enough transmitter substance to effect synaptic transmission has been challenged by Koelle (1961Koelle ( , 1962). Koelle's hypothesis is that, at cholinergic synapses, a nerve impulse releases too little acetylcholine (ACh) to stimulate the postganglionic cell directly, but enough to prolong the state of depolarization of the presynaptic nerve terminals so that they discharge additional ACh which does effect transmission.This suggestion that there is a positive feed-back mechanism for release implies that exogenously applied ACh, or ACh-like agent, should release transmitter from presynaptic nerve endings, and some evidence has accumulated that this might be