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

Abstract

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.

Patch‐clamp analysis of glycine‐induced currents in chick ciliary ganglion neurons.

“…Similar results were obtained here with ciliary ganglion GlyRs. dTC, which blocks AChRs at micromolar concentrations, also blocks GABA responses in frog spinal cord neurons (Nicoll, 1975;Bixby & Spitzer, 1984) and ciliary ganglion GlyRs, as shown here, when used at high concentrations. Strychnine has much greater affinity for GlyRs than for GABAA receptors (e.g.…”

“…Bicuculline is a competitive antagonist of GABAA receptors, but its specificity has been questioned (Hill, Simmonds & Straughan, 1976;Zhang & Feltz, 1991 (Nicoll, 1975;Hill et al 1976;Lebeda, Hablitz & Johnston, 1982;Bixby & Spitzer, 1984). dTC inhibited responses induced by 40 /M glycine from ciliary ganglion neurons in a dose-dependent manner (Fig.…”

Convulsant and Possible Anticholinergic Actions of Dendrotoxin in the Amphibian Spinal Cord

“…When indirect responses were blocked by using 2 mM Mn2+/0.4 mM Ca2' Ringer (cf. Nicoll, 1975), carbachol or ACh produced only small and variable responses on VR or DR. These responses, presumably resulting from activation of acetylcholine receptors on primary afferents or motoneurones, were not completely antagonized by DHj3E.…”

“…Neither mecamylamine, a-bungarotoxin nor atropine showed any tendency to induce DTOXlike convulsant activity. Although (+)-tubocurarine is known to promote convulsant activity in the isolated spinal cord of the frog, this is probably due to an anti-GABAergic rather than anticholinergic action of the drug (Nicoll, 1975).…”

“…This is consistent with an action of the toxin on nicotinic receptors; however, it does not prove that this is the site of toxin action because of the indirect nature of these responses (cf. Nicoll, 1975). DTOX 6 could be antagonizing the carbachol response at any point between the cholinoceptive neurones and the ventral and dorsal roots.…”