Yoshihisa Kudo

The chloride-dependent depression by GABA in the frog spinal cord☆

Spontaneous activities from ventral and dorsal roots of the isolated perfused spinal cord of the bullfrog were inhibited by GABA. beta-Alanine showed a strong and glycine a weaker inhibitory effect. The inhibitory effect of GABA was markedly reduced in a chloride-free medium, whereas glycine and beta-alanine still showed an inhibitory effect similar to that seen in normal medium. Employing the sucrose-gap method, a marked depolarization in the dorsal root and a small but obvious hyperpolarization in the ventral root were found by the application of GABA. These results support the view that GABA is one of the transmitters involved in pre- and postsynaptic inhibition of the spinal cord. The postsynaptic hyperpolarizing effect of GABA on motoneurones would be caused directly through increased permeability of the membrane to chloride ion. The depolarizing effect of GABA on primary afferent terminals is discussed in connection with chloride dependency.

Mechanisms of depressant action of baclofen on the spinal reflex in the rat

Abstract The experiments were performed on spinal rats transected at Cl level. Baclofen (2 mg/kg, i.v.) produced a significant reduction in monosynaptic reflex (MSR), dorsal root potential (DRP) and focal synaptic potential without affecting resting DRP, post-tetanic hyperpolarization in the dorsal root and excitability of the primary afferent fiber and the motoneuron soma. Mephenesin (50 mg/kg, i.v.) reduced MSR, DRP and excitability of the primary afferent fiber and motoneuron soma, but did not change post-tetanic hyperpolarization in the dorsal root or focal synaptic potential. These findings suggest that the depression of the spinal cord by baclofen is due to either reduction of transmitter release from the primary afferent terminal or antagonism of the action of the transmitter(s) released from the terminal. It is also suggested that the effect of mephenesin may be attributable to stabilization of the motoneuron membrane, and resulting inhibition of the spike generation.

An apparent excitatory action of baclofen on the isolated perfused spinal cord of the frog

Abstract 1. 1. Baclofen (10−5−10−4 M) caused a hyperpolarization in both dorsal and ventral roots of the frog spinal cord. 2. 2. The peak amplitude of dorsal root potential was reduced only slightly, while its rise time was markedly prolonged. 3. 3. The ventral root potential evoked by a high voltage stimulation (more than 5 V) was augmented, while the first spike potential was abolished. 4. 4. The rise time of excitatory postsynaptic potential and the latent period for the initiation of action potential were prolonged. 5. 5. The mechanisms of action of baclofen were discussed based upon these results.

Dual effects of acetylcholine on the spontaneous activity in the isolated perfused spinal cord of the frog.

Abstract This study was undertaken to elucidate the possible cholinergic mechanisms contributing to the excitation of spinal motoneurones. Experiments were carried out in isolated spinal cord-nervemuscle preparations of the bullfrog, in which the spinal cord was perfused with Ringer solution through the anterior spinal artery. The spontaneous discharges on the ventral root and the muscle contractions were recorded simultaneously. The addition of acetylcholine (10−4-10−3m) to the medium, perfusig the spinal cord, resulted in a transient increase in the rate of spontaneous discharges in the ventral root accompanied by tonic muscle contractions. The effect was inhibited by d-tubocurarine (10−5M) but not by atropine (10−5 M). Nicotine (10−5 M) caused a marked increase in the rate of spontaneous discharges and tonic muscle contractions. With continuous application of acetylcholine, spontaneous discharges in the ventral root sometimes changed to rhythmical bursts. Carbamylcholine (10−5M), bethanechol (10−4M) and methacholine (10−3M) clearly induced the rhythmical bursts and corresponding muscle contractions. The initiation of the rhythmic activity was prohibited by pretreatment with atropine (10−5M). The results suggest that there are at least two types of cholinergic synapses in the frog spinal cord; muscarinic and nicotinic.

Antagonistic action of baclofen on substance P-induced depolarization in the isolated spinal cord of the frog

Abstract 1. 1. The depolarization induced by substance P (2 × 10 −8 mol) on the ventral root of the isolated frog spinal cord was not affected by baclofen (10 −4 M) in the normal medium, whereas the depolarization in the tetrodotoxin-treated or Ca 2+ -free, 1.8 mM Mg 2+ medium-perfused preparation was significantly reduced by baclofen. 2. 2. The depolarization induced by l -glutamate (2 × 10 −7 mol) was not affected by baclofen in normal and also in TTX- or Ca 2+ -free, 1.8 mM Mg 2+ -treated preparation. 3. 3. The results suggest that baclofen specifically antagonizes the depolarization induced by substance P at postsynaptic membrane.

The effect of diazepam on nystagmus induced by stimulation of the lateral geniculate body in the rabbit

Abstract The effect of diazepam on central nystagmus elicited by unilateral stimulation of the lateral geniculate body in the rabbit was studied. Diazepam (1 mg/kg i.v.) slightly decreased the beat number of the nystagmus during the stimulation period and remarkably prolonged the after-nystagmus. Picrotoxin (0.6 mg/kg i.v.) completely antagonized the facilitatory effect of diazepam on the after-nystagmus, but not the inhibitory effect on the nystagmus. After treatment with semicarbazide-HCl (200 mg/kg i.v.), diazepam had no effect on the after-nystagmus. These results suggest that diazepam may act on central nystagmus through mechanisms mediated by GABA.

Excitation of rat muscle spindle afferents by lyoniol-A

Abstract The effect of lyoniol-A, a diterpenoid from an Ericaceous plant, on the de-efferented muscle spindle was studied to elucidate the mechanism responsible for abnormal behaviours in mammals resulting from administration of the agent. Increase in the frequency of afferent discharges in response to lyoniol-A (200–300 Hz) was much greater than that obtained on stretching the muscle or after suxamethonium. The result showed that lyoniol-A did not affect the extrafusal fibres nor intrafusal fibres and that adaptation, one of the characteristics of a muscle spindle, did not appear after an administration of the agent. In conclusion, lyoniol-A is a potent muscle spindle excitant that is likely to be a pharmacologically useful tool, and this action may largely responsible for the abnormal behaviours resulting from an administration of lyoniol-A. The experiment also dealt with lyoniol-B (deacetyl-lyoniol-A), grayanotoxin-I and veratridine.

Depression by strychnine of afferent discharges from the muscle spindle of the bullfrog in vitro

Abstract Strychnine (1.25 × 10−5 − 1 × 10−4M) caused a reduction in the rate of afferent discharge from the muscle spindle of the isolated M. extensor longus dig. IV from the bullfrog subjected to stretch. The possible site of action of the drug is discussed.