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Biomedical subjects

J L Barker

Publications and source records attributed to J L Barker.

At least 19 recordsLinked to original sources
PubMed1979

Phenobarbitone modulation of postsynaptic GABA receptor function on cultured mammalian neurons.

The anticonvulsant barbiturate phenobarbitone increases membrane current and conductance responses to gamma-aminobutyric acid (GABA) in cultured mouse spinal neurons. Analyses of GABA current fluctuations under control conditions and in the presence of phenobarbitone show that the principle action is to increase the average time during which GABA-activated channels remain open. The duration of minature synaptic currents with a time constant of decay similar to the mean open-time of GABA-activated channels is prolonged by the drug. The results suggest that (1) the synaptic events are GABA-mediated and (2) the enhancement of these events by barbiturate is due to the postsynaptic action of the drug.

Animals↗
PubMed1979

Substance P: evidence for diverse roles in neuronal function from cultured mouse spinal neurons.

Mouse spinal neurons grown in tissue culture were used to examine the membrane mechanisms of action of the peptide substance P. Two functionally distinct actions were observed, one being a rapidly desensitizing excitation, and the other being a dose-dependent, reversible depression of excitatory responses to the putative amino acid neurotransmitter glutamate. These effects on excitability suggest that substance P may play more than one role in intercellular communication in the nervous system.

Animals↗
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

Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of anticonvulsant action.

Murine spinal cord neurons grown in dissociated cell culture were used to study the effects of barbiturate (phenobarbital, mephobarbital) and benzodiazepine (diazepam, chlordiazepoxide( anticonvulsants on amino acid responses. Both types of anticonvulsant augmented GABA-mediated postsynaptic inhibition without augmenting beta-alanine or glycine-mediated postsynaptic inhibition. Barbiturates, but not benzodiazepines, antagonized glutamate-mediated postsynaptic excitation. Augmentation of GABA-mediated inhibition by the anticonvulsants should contribute to their anticonvulsant action; antagonism of glutamate-mediated excitation by barbiturates should also contribute to their anticonvulsant action and could be at least in part responsible for their sedative actions.

Animals↗
PubMed1979

Conservation surgery and irradiation for the treatment of favorable breast cancer.

The results in 162 patients with clinically favorable breast cancer treated with conservation surgery and radiation therapy are presented. The surgical procedures were simple excision with and without positive microscopic margins, segmental mastectomy, and segmental mastectomy with axillary dissection. Details of the radiation techniques are described with an explanation of the modifications in technique depending on the prior surgical procedure. Excellent control of local and regional tumor (96%) gives support to the combined treatment without removing the breast.

Adult↗
PubMed1979

Anticonvulsant and anesthetic barbiturates: different postsynaptic actions in cultured mammalian neurons.

Mammalian spinal cord neurons were grown in dissociated cell culture and used to study the effects of the anticonvulsant barbiturates phenobarbital and mephobarbital, and the anesthetic barbiturates pentobarbital, secobarbital, and 1,3-dimethyl-butylethyl barbituric acid on amino acid responses and neuronal membrane properties. All barbiturates augmented responses to GABA and diminished glutamate (GLU) responses, but the anesthetic barbiturates were more potent. The anesthetic barbiturates directly depressed excitability by increasing membrane conductance, an effect reversed by the GABA antagonists picrotoxin and penicillin. Anticonvulsant barbiturates, however, had only minimal GABA-mimetic inhibitory action at high doses. Modulation of synaptic events mediated by GABA and GLU might contribute to barbiturate anticonvulsant activity; and direct GABA-mimetic inhibition, combined with similar modulation of synaptic transmission, might underlie barbiturate anesthesia.

Animals↗
PubMed1978

Enkephalin-containing neurons visualized in spinal cord cell cultures.

Neuronal cells, axons, and terminals containing immunoreactive enkephalin have been visualized in cultures of dissociated fetal spinal cord. These cultures may provide a valuable system in which to explore the effects of chronic drug treatment on the physiology of enkephalin-containing cells and their interactions with other cells.

Animals↗
PubMed1978

Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons.

Barbiturate anesthetics, but not anticonvulsants, abolish the spontaneous activity of cultured spinal cord neurons; directly increase membrane conductance, an effect which is suppressed by the gamma-aminobutyric acid (GABA) antagonists picrotoxin and penicillin; and are more potent than anticonvulsants in augmenting GABA and depressing glutamate responses. Barbiturate anticonvulsants abolish picrotoxin-induced convulsive activity. These results indicate qualitative and quantitative differences between anesthetic and anticonvulsant barbiturates, which may explain their different clinical effects.

Action Potentials↗
PubMed1978

Opiate peptide modulation of amino acid responses suggests novel form of neuronal communication.

Mouse spinal neurons grown in tissue culture were used to study the electrophysiological pharmacology of the opiate peptide leucine-enkephalin. Enkephalin depressed glutamate-evoked responses in a noncompetitive manner independent of any other effects on membrane properties. The results demonstrate a neuromodulatory action of opiate peptide functionally distinct from the conventional neurotransmitter class of operation.

Cells, Cultured↗
PubMed1978

Amino acid pharmacology of mammalian central neurones grown in tissue culture.

1. Spinal and cerebellar-brainstem areas of fetal mouse were dissociated and grown in tissue culture until large enough to permit stable intracellular recording. 2. The tissue-cultured neurones, growing as a monolayer and accessible under direct vision using phase contrast optics, allowed precise placement of intracellular recording and extracellular ionophoretic pipettes. 3. Ionophoresis of GABA and glutamate revealed a non-uniform distribution of responses over the cell surface, with a lack of spatial coincidence in sensitivity between the two. GABA inhibited and glutamate excited all cells tested. 4. GABA responses evoked at the cell body and on nearby process membrane were almost uniformly hyperpolarizing, while those at some peripheral process membrane were either hyperpolarizing, depolarizing or a combination of both events. All responses were associated with an increase in membrane slope conductance. 5. Membrane polarization showed that all hyperpolarizing events extrapolated to about the same inversion potential, which averaged about 9 mV more negative than resting potential (n = 95 cells). The depolarizing phases of responses evoked at peripheral membranes extrapolated to about 0 mV (n = 5 cells). 6. The hyperpolarization and increase in membrane conductance of GABA responses at the cell body were dependent on Cl- ions and the inversion potential of the response was dependent on the Cl- ion concentration gradient. The inversion potentials of GABA, glycine and beta-alanine responses were identical. 7. When matched in magnitude for evoked conductance increase, glycine responses decayed more rapidly than GABA. Glycine and beta-alanine voltage responses both decayed faster than GABA responses of comparable size. 8. In about half the cells tested sustained or rapidly repeated application of GABA and glycine transformed hyperpolarizing responses into depolarizations which were associated with a maintained conductance increase. Results from conditioning-test experiments with pairs of GABA and glycine responses suggest that the reversal of response polarity is due to a rapid redistribution of Cl- ions. 9. The limiting slope of log-log dose-response curves for GABA-induced conductance averaged about 2, while those for glutamate-induced depolarizations averaged about 1. The results suggest that two molecules of GABA and one molecule of glutamate participate in the respective post-synaptic responses. 10. The observation indicate that mammalian C.N.S. tissue grown in culture is a suitable model to study C.N.S. membrane pharmacology with increasing precision.

Alanine↗
PubMed1978

Pentobarbitone pharmacology of mammalian central neurones grown in tissue culture.

1. The effects of the barbiturate anaesthetic pentobarbitone on the membrane properties and amino acid pharmacology of mammalian C.N.S. neurones grown in tissue culture were studied using intracellular recording coupled with bath application, extracellular ionophoresis, or focal diffusion. 2. The addition of an anaesthetic concentration of pentobarbitone to the bathing medium abolished all spontaneous synaptic activity, but did not render individual cells electrically inexcitable nor prevent evoked synaptic acitivity. 3. Focal ionophoresis of pentobarbitone or diffusion from blunt micropipettes reversibly increased membrane conductance, effectively dampening excitability without directly affecting individual action potential characteristics. 4. Pentobarbitone-induced membrane conductance was reversibly blocked by picrotoxin. The inversion potential of the pentobarbitone voltage response depended on Cl- ion gradients and was similar to that of GABA. 5. Pentobarbitone reversibly enhanced the conductance increase produced by GABA with a variable slowing of response kinetics, shifting GABA dose-response curves to the left. Responses to glycine and beta-alanine were not affected. 6. Higher ionophoretic currents of pentobarbitone, which measurably increased membrane conductance, attenuated and markedly slowed GABA responses. Similar effects on GABA responses were observed by superimposing GABA pulses on low level GABA currents. 7. Pentobarbitone, in the absence of an increase in membrane conductance, reversibly depressed depolarizing responses to glutamate without changing response kinetics. Slower responses to acetylcholine which were associated with an apparent decrease in membrane conductance were not affected by the drug. 8. Analysis of double-reciprocal plot data suggested a non-competitive type of antagonism between pentobarbitone and glutamate. Pentobarbitone depression of glutamate was not affected by picrotoxin. 9. Both GABA and glutamate responses appeared to be equally sensitive to pentobarbitone. Specific interaction of the drug with amino acid receptor-coupled events is indicated by the requirement for pentobarbitone pipette placement close to the amino acid response site. 10. The results suggest that pentobarbitone depresses neuronal excitability by (1) directly activating post-synaptic GABA-receptor coupled Cl- conductance, (2) potentiating post-synaptic GABA-induced conductance events, probably at the level of the GABA receptor, and (3) depressing post-synaptic glutamate-induced excitation, probably at the level of the conductance mechanism.

Animals↗
PubMed1978

Specific antagonism of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of convulsant action.

Mammalian spinal neurons grown in tissue culture were used to study the effects of the four convulsants-penicillin, pentylenetetrazol, picrotoxin, and bicuculline-on these neurons' responses to amino acids. Bath application of all four convulsants produced paroxysmal depolarizing events in the neurons; iontophoresis of the four convulsants selectively depressed responses produced by iontophoresis of the putative inhibitory transmitter GABA, and effected this depression without altering either inhibitory responses to beta-alanine or glycine, or excitation mediated by glutamate. These results support the hypothesis that the convulsant activity of these agents comes in part from selective antagonism of GABA-mediated postsynaptic inhibition.

Amino Acids↗