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Biomedical subjects

J F MacDonald

Publications and source records attributed to J F MacDonald.

13 recordsLinked to original sources
PubMed1979

Inosine may be an endogenous ligand for benzodiazepine receptors on cultured spinal neurons.

Mouse spinal neurons grown in tissue culture were used to study the membrane effects of the benzodiazepine flurazepam and the naturally occurring purine nucleoside inosine, which competes for benzodiazepine receptor sites in the central nervous system. Application of inosine elicited two types of transmitter-like membrane effects: a rapidly desensitizing excitatory response and a nondesensitizing inhibitory response. Flurazepam produced a similar excitatory response which showed cross-desensitization with the purine excitation. Flurazepam also blocked the inhibitory inosine response. The results provide electrophysiological evidence that an endogenous purine can activate two different conductances on spinal neurons and that flurazepam can activate one of the conductances and antagonize the other.

Animals↗
PubMed1979

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. The prominent after-hyperpolarization (a.h.p.), which normally follows the motoneuronal action potential, was consistently and reversibly depressed by Mn and Co (as well as La), the underlying conductance increase being also diminished, but there was no significant reduction in the after-depolarization. By contrast, Sr tended to potentiate the a.h.p., especially when this was depressed by a previous injection of Co or Mn. Unlike the other cations, Co had a marked depressant effect on the action potential, particularly its rate of rise. Since the action potential could be immediately restored by hyperpolarization or by an injection of Sr (in the absence of depolarization), Co may enhance Na inactivation.

Action Potentials↗
PubMed1979

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.) as well as its underlying conductance increase. There is also an increase in excitability, sometimes leading to outright discharge, and a change in the current-firing relation: the normal primary range is largely abolished and the firing appears to have the characteristics of the normal secondary range. Intracellular effects of Mg are thus mainly opposite to those of Ca, possibly owing to competition at sites where Ca activates K channels. Intracellular injections of Mn also tend to depress the a.h.p. but have relatively little effect on resting potential and conductance, or action potentials. Co also depresses the a.h.p. but has a more pronounced depolarizing action, and produces particularly strong depression of action potentials. By contrast intracellular Sr tends to raise the membrane conductance and has a mild hyperpolarizing effect. During the injection of Sr, a.h.p's are depressed but this is followed by a rebound of increased a.h.p. amplitude and conductance. Unlike the other divalent cations tested, Sr strongly depressed excitatory postsynaptic potentials. In most respects Sr appears to behave like Ca.

Action Potentials↗
PubMed1978

A comparison of the action of glutamate, ibotenate and other related amino acids on feline spinal interneurones.

1. The effects of microiontophoretically applied glutamate, ibotenate and other related amino acids on the spike activity of feline spinal interneurones were investigated. 2. Unlike the other amino acids, which evoked excitatory responses only, ibotenate evoked slow biphasic responses (excitation-depression) from the majority of these neurones. The depressant action was associated with an increase in spike height and was reversible. 3. The ibotenate depression could be observed as a temporary reduction in background firing rate, a loss of sensitivity to other amino acids, a progressive decrease in the excitatory responses to repetitive ibotenate applications or a fading of excitation following a prolonged administration of ibotenate. 4. The onset of the excitatory effects of glutamate, quisqualate and ibotenate was relatively well fitted by diffusion equations for a continuous point source. However, radial distances for diffusion in the case of ibotenate responses were comparatively greater than those for glutamate and quisqualate. 5. The depressant action of ibotenate was not antagonized by strychnine, picrotoxin or bicuculline. 6. Some methods of quantifying the responses to excitatory amino acids are described. The excitatory potency of quisqualate and N-methyl-D-aspartate was several times greater than that of glutamate. Aspartate and ibotenate were equipotent, while alpha-aminopimelate and alpha-methyl-DL-aspartate were much weaker. 7. It is suggested that the biphasic action of ibotenate on spinal interneurones might be the result of activation of excitatory and inhibitory sites fairly remote from the cell somata where extracellular recordings were probably made.

Action Potentials↗
PubMed1978

Motoneuronal after-potentials and extracellular divalent cations.

In cats under Dial anesthesia, microiontophoretic injections of Co2+ or Mn2+ outside lumbosacral motoneurones regularly diminish the postspike hyperpolarizing after-potential (AHP) without any clear reduction of the deplorarizing after-potential (ADP). Comparable injections of Sr2+ have the opposite effect of augmenting the AHP. These results indicate that the AHP is indeed initiated by an influx of calcium linked to the action potential, but the ADP is unlikely to be mainly a manifestation of a calcium inward current.

Action Potentials↗
PubMed1978

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. It is concluded that changes in intracellular levels of monoamines, whether physiological or drug induced, may be of significance for central neuronal function.

Action Potentials↗
PubMed1977

A progressive and cumulative suppression of the activity of spinal neurones in the nonspinal rat.

Electrical stimulation of the skin of the hindpaw of the rat, at frequencies ranging from 2 to 0.2 s-1, halted the tonic or evoked activity of spinal neurones. The duration of this effect increased with each successive stimulus until it outlasted the interstimulus interval. Tonic activity did not return immediately following termination of the stimulation, and activity was often depressed for periods of up to 5 min. Neurones displaying this behaviour were found in laminae 1 and 4--7 of the cord. Some neurones failed to demonstrate this behaviour following the administration of strychnine. This phenomenon provides a possible substrate for habituation of the flexor reflex that occurs with repetitive and noxious stimulation of the skin.

Action Potentials↗
PubMed1977

Actions of microiontophoretically applied ibotenate on cat spinal interneurones.

Microiontophoretic applications of ibotenate, an amino acid analogue of glutamate, evoked biphasic responses from single dorsal horn interneurones of the cat spinal cord, i.e., an initial increase in the firing rate followed by a sustained depression of spontaneous firing. A reduced cell sensitivity to excitatory amino acids or peripheral field stimulation was also found during the ibotenate-induced depression. These effects were not produced by glutamate, quisqualate, or kainate, although occasional transient reductions of spontaneous cell firing were observed after application of glutamate. It is suggested that ibotenate might act on inhibitory as well as excitatory receptors of cat spinal interneurons.

Action Potentials↗
PubMed1977

Neuronal depressant effects of diethylester derivatives of excitatory amino acids.

The effect of iontophoretically applied kainic acid diethylester (KDEE) on the firing rate of feline spinal interneurones was investigated and compared with the action of glutamic acid diethyles (GDEE) and aspartic acid diethylester (ADEE). All these esters reversibly reduced spontaneous neuronal firing and increased spike height, KDEE being the most active of this group. KDEE decreased response to glutamate, acetylcholine, and peripheral field stimulation, showing that its depressant action is not due to a selective antagonism of an excitatory putative transmitter.

Acetylcholine↗