Influence of caffeine and midazolam on gamma-aminobutyric acid-evoked responses in the frog spinal cord.

The recently reported potentiation of gamma-aminobutyric acid (GABA) evoked depolarizations by caffeine in the frog spinal cord might involve an interaction with GABA-linked benzodiazepine receptors. This possibility was investigated using a new potent benzodiazepine, midazolam, and a benzodiazepine antagonist, Ro 147437. Caffeine or midazolam enhanced the amplitude of submaximal GABA responses by about 50%; when equieffective enhancing doses of these compounds were simultaneously applied, GABA depolarizations were usually depressed below control levels.

Potentiating action of midazolam on GABA-mediated responses and its antagonism by Ro 14-7437 in the frog spinal cord.

The effect of midazolam, a new water-soluble benzodiazepine, on an in vitro slice preparation of the frog spinal cord was investigated using electrophysiological recordings. Midazolam potently (ED50 = 1 nM) enhanced the depolarizing action of GABA on primary afferent fibres while leaving the depolarizing effect of glutamate, glycine or high K+ solutions unchanged. Concentrations of midazolam higher than 100 nM had an antagonistic effect on GABA responses.

Caffeine-induced potentiation of GABA effects on frog spinal cord: an electrophysiological study.

A parasagittal slice of the frog spinal cord was kept in vitro for electrophysiological recordings from dorsal and ventral roots. Low concentrations of caffeine (50 microM) which had relatively small effects on baseline electrical activity, increased the depolarizing action of GABA on dorsal root fibres by 50%. A similar result was also obtained when GABA motoneuronal responses were tested.

Differential sensitivity of spinal neurones to amino acids: an intracellular study on the frog spinal cord.

Intracellular recordings from in vitro neurones of the frog spinal cord slice preparation were performed in order to examine the mechanism of action of gamma-aminobutyrate and glutamate on two distinct neuronal populations in the same region of the central nervous system. Amino acids were superfused at fast rate and low temperature (7 degrees C) to reduce their uptake process. On interneurones, the inhibitory action of gamma-aminobutyrate was characterized by a large input conductance increase while on motoneurones the conductance change was much smaller.

The effects of piperazine on rat sympathetic neurones.

1. The neuronal effects of the anthelmintic piperazine (Pip) on rat sympathetic ganglia were studied in vitro by means of intracellular and extracellular recording techniques. 2.

Excitatory and inhibitory action of ibotenic acid on frog spinal motoneurones in vitro.

Ibotenic acid (IBO), a conformationally-restricted analogue of the putative excitatory transmitter glutamate, produced biphasic effects on frog spinal motoneurones recorded wih DC-coupled Ag/AgCl electrodes placed on the central end of ventral roots. The initial effect consisted of a motoneuronal depolarization with an increase in excitability tested with low-intensity dorsal root stimulation (the depolarizing activity of IBO was about 6 times greater than that of glutamate). On washout, the depolarizing effect of IBO subsided and complete motoneuronal repolarization occurred; however, motoneuronal responses to glutamate and to trans-synaptic stimulation remained depressed for prolonged periods.

Intracellularly-recorded effects of glutamate and aspartate on neurones in the guinea-pig olfactory cortex slice.

The effects of bath-applied glutamate, aspartate (and some related amino acids) on neurones of the guinea pig olfactory cortex slice were recorded intracellularly. Neurones were activated either by intracellularly-applied current or orthodromically by stimulating the lateral olfactory tract. In response to orthodromic stimuli several neurones displayed a late hyperpolarizing potential (LHP) after the usual sequence of EPSP, spike and IPSP.

Intraneuronal effects of inhibitory amino acids.

Injections of gamma-aminobutyric acid (GABA) into spinal motoneurons (in cats under Dial) induce a small but relatively prolonged hyperpolarization (mean - 1.7 mV, SD 2.1; n = 25) which is associated with a rise in input resistance (mean 44%, SD 122; n = 34), is not reversed by hyperpolarization, and is not potentiated by intracellular release of benzodiazepines.

Effects of microiontophoretically applied flurazepam on responses of cerebral cortical neurones to putative neurotransmitters.

Utilizing standard microiontophoretic techniques and recording extracellularly in cats, we studied the effects of flurazepam, a water-soluble benzodiazepine, on the spike activity of single cerebral neurones and its interactions with several excitatory and inhibitory putative neurotransmitters. Large iontophoretic doses (5--30 nA, 0.1 M solution) of flurazepam induced a depression of spike amplitude.

Effects of some divalent cations on motoneurones in cats.

In cats under Dial, Co, Mn, La, and Sr were injected extracellularly near lumbosacral motoneurones. All tended to improve intracellular recording, but when the membrane potential was initially stable, Mn, and especially Co, had a moderate and reproducible depolarizing action. Both Mn and Co depressed excitatory postsynaptic potentials evoked by dorsal root stimulation.

Intracellular divalent cations and neuronal excitability.

Itracellular injections of Mg into cat spinal motoneurones have a depolarizing action, associated with a fall in input conductance, and depression of the postspike hyperpolarizing after-potential (a.h.p.

Further observations on the interaction between glutamate and aspartate on lobster muscle.

1 The ability of bath-applied L-glutamate to enhance subsequent depolarizations produced by bath-applied L-aspartate on lobster muscle was further investigated by means of intracellular recording techniques. 2. Increasing the conditioning glutamate concentration or exposure time produced a greater enhancement of aspartate responses.

Intracellular actions of monoamine transmitters.

Intracellular injections of noradrenaline or dopamine in spinal motoneurones of cats have a clear depolarizing action associated with particularly marked depression of spike potentials and their after-hyperpolarization, but with little slowing-down of the falling phase of the action potential. These effects are associated with an increase in input resistance, and they are reversible and reproducible in the same neurone. Intracellular injections of 5-hydroxytryptamine have some depolarizing action and increased input resistance, but they produced no comparable depression of the action potential and tended to enhance the after-potentials and increase excitability.

A presynaptic component of the action of iontophoretically applied flurazepam on feline cortical neurones.

The effect of iontophoretically applied flurazepam on the spike activity of pericruciate cortical neurones of the cat was studied. Flurazepam increased cortical inhibition produced either by local electrical stimulation (which is known to release gamma-aminobutyric acid (GABA) or by iontophoretically applied GABA. Following intravenous treatment with thiosemicarbazide (a GABA-synthesis inhibitor), flurazepam still augmented the action of GABA but was much less effective on electrically evoked cortical inhibition.