Analysis of amino acid responses on frog motoneurones

Self Cite

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: 92%

Section: Methodsmentioning

confidence: 99%

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

NICOLL

1975

Self Cite

“…Nicoll et al, 1976;Barker & Ransom, 1978;Obata et al, 1978). It has been disputed whether the components of this biphasic response are generated by the same ionic channel or by separate ionic channels.…”

Section: Discussionmentioning

confidence: 99%

Possible involvement of K⁺‐conductance in the action of γ‐aminobutyric acid in the guinea‐pig hippocampus

Inoue

Matsuo

Ogata

1985

1 The mechanism underlying the action of y-aminobutyric acid (GABA) in the hippocampus was investigated using guinea-pig brain slices. 2 GABA either superfused or applied directly by microiontophoresis produced a biphasic response in pyramidal cells, comprising hyperpolarizing and depolarizing components. 3 When different concentrations of GABA were applied to the same neurone, the lower concentrations generally produced a hyperpolarization-predominant response, while higher concentrations resulted in a depolarization-predominant response. 4 The depolarizing component of the response to GABA was augmented in a medium containing a low concentration ofCl-, relatively unaffected by a change in external K+ concentration, and blocked by picrotoxin (2 x 10-5 M). The depolarizing response to GABA persisted in a Ca2+-free medium in which the concentration of Na+ was reduced to 13 mM. 5 Combined application of low doses of picrotoxin and bicuculline eliminated the major part of the depolarizing component of the biphasic response to GABA and produced a relatively pure hyperpolarizing response. The reversal potential of this pharmacologically 'isolated' hyperpolarizing response to GABA was estimated, from the current-voltage relationships, to be about -90 mV and was the same as that of the hyperpolarization induced by baclofen. 6 When the membrane was successively hyperpolarized by inward direct current (d.c.) injections, the reversal point of the 'pharmacologically isolated' hyperpolarizing response to GABA coincided with that of the post-burst hyperpolarization. 7 Low concentrations of Cl-in the bathing medium had no noticeable effect on the hyperpolarizing component of the response to GABA, whereas it markedly increased the amplitude of the depolarizing component.8 These results suggest that the action of GABA in the hippocampus may involve an activation of K+ conductance.

“…For example, glutamate increases the activity of both types of cell, but with a great difference in effective dose. Glycine is best known as causing strychninesensitive hyperpolarization and inhibition in spinal cord neurones; but it may also cause strychnineresistant depolarization probably leading to excitation (Nicoll, Padjen & Barker, 1976;Evans, Francis & Watkins, 1976), which corresponds more closely with its myometrial effect. The myometrium-stimulating potencies of various amino acids show a better correlation with their rates of metabolism by brain slices than with their uptake (Sadasivudu & Lajtha, 1970).…”

Section: Discussionmentioning

confidence: 99%

Spasmogenic and Potentiating Actions of Some Amino Acids on the Guinea‐pig Myometrium

Bedwani

Ishizawa

Pickles

et al. 1977

I Thirty-three amino acids were applied separately in concentrations of 2 to 10 mM to guinea-pig uterine horns in vitro at pH 7.4. About half the acids regularly produced contractions. 2 Glycine and the straight-chain L-a-amino acids up to norleucine were active (longer ones not tested); D-isomers were less potent or inactive in these concentrations. The co-amino acids yaminobutyric acid (GABA) and 6-aminovaleric, and the a,o-diamino acids L-a, P-diaminopropionic and L-a,y-diaminobutyric were active, whereas others of similar chain-length such as f,-alanine and lysine were not. The diacidic acids, glutamic and homocysteic, were more active than the amido-amino acids, glutamine and asparagine. Histidine and phenylalanine showed little or no activity. 3 The use of appropriate blocking agents indicated that the responses to representative acids were not mediated by histamine, 5-hydroxytryptamine, acetylcholine, noradrenaline or by prostaglandins. Attempts to block the actions of glycine and GABA with strychnine, thebaine, picrotoxin, bicuculline or tetramethylenedisulphotetramine (TETS) were unsuccessful. 4 When some of the acids that were spasmogenic at 2 to 10 mm were applied at sub-spasmogenic doses, they transiently potentiated other spasmogens such as oxytocin or acetylcholine. This effect was also shown by a mixture of amino acids at approximately the normal plasma concentrations. 5 There is some similarity between the spasmogenic activities of different amino acids and their known abilities to depolarize neurones.