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C D Richards

Publications and source records attributed to C D Richards.

123 records · Page 7Linked to original sources

On the mechanism of barbiturate anaesthesia.

1. The effects of pentobarbitone (0.05-0.6 mM in saline solution) on the evoked field potentials of in vitro preparations of guinea-pig olfactory cortex were studied.2. The evoked field potentials comprised an initial diphasic wave - the lateral olfactory tract (l.o.t.) compound action potential - followed by a surface negative wave (e.p.s.p) of 1-3 mV amplitude and about 10 msec duration. Superimposed on the negative wave were a number of positive peaks (population spikes).3. Pentobarbitone depressed the e.p.s.p. but not the l.o.t. compound action potential. The number and size of the population spikes were progressively reduced as the e.p.s.p. became depressed, indicating a failure of transmission through the cortical relay. The e.p.s.p. depression increased with increasing concentrations of pentobarbitone.4. Pentobarbitone had no effect on the threshold to electrical stimulation of the l.o.t. fibres or on that of the post-synaptic cells to synaptic excitation.5. Post-tetanic potentiation and frequency potentiation were either of normal magnitude or were enhanced in the presence of 0.2-0.3 mM pentobarbitone.6. It is concluded that pentobarbitone probably reduces the output of transmitter from the presynaptic nerve terminals of the olfactory cortex and that this mechanism could be the basis of the depressant action of the barbiturates.

Action Potentials↗

Calcium, magnesium and the electrical activity of guinea-pig olfactory coex in vitro.

1. Evoked electrical activity was observed in slices from guinea-pig olfactory cortex maintained in vitro. This evoked activity was studied in saline solutions containing various concentrations of Ca(2+) and Mg(2+).2. The evoked potentials recorded from the surface of the prepiriform cortex comprised a negative wave (N-wave) of about 10-15 msec duration upon which a variable number of short duration positive notches were superimposed. The N-wave was identified as a population excitatory post-synaptic potential (EPSP) of the olfactory cortex neurones and the positive notches were identified with synchronous discharge of cortical neurones.3. The relation between the EPSP amplitude and saline Ca(2+) concentration was sigmoid. The N-wave amplitude (EPSP) was proportional to [Ca(2+)](o) (n). When saline Ca(2+) was between 0.4 and 1 mMn averaged 2.5 (range 1.5-4.3).4. The EPSP amplitude was reduced by increasing saline [Mg(2+)]. High Mg(2+) salines (about 10 mM) abolished the EPSP.5. Both Ca(2+) and Mg(2+) in high concentrations depressed the positive notches.6. Salines containing little or no Ca(2+) and Mg(2+) caused the preparation to show signs of hyperexcitability. Under these conditions the evoked potentials were very variable and unstable. ;Ca(2+)-free' salines caused a reversible loss of excitability.7. The results indicated that Ca(2+) and Mg(2+) had antagonistic effects on the release of the transmitter substance(s). Increased Ca(2+) concentrations increased the output of transmitter, increased Mg(2+) concentrations reduced the output of transmitter. Both Ca(2+) and Mg(2+) in increasing concentration increased the threshold for action potential generation.

Action Potentials↗

Chloride fluxes in crab muscle fibres.

1. Isotopic techniques were used to study the efflux of Cl(-) from single cannulated muscle fibres of the crab Maia squinado.2. The efflux of (36)Cl(-) was found to be exponential with steady rate constants ranging from 0.01 to 0.07 min(-1). The steady efflux was ca. 1000-2000 pM cm(-2) sec(-1). The efflux was slightly depressed by K(+)-free saline and was unaffected by 40 mM-K(+) saline and NO(3) (-) saline. The influx and efflux of Cl(-) were presumed independent.3. The membrane conductance calculated from (36)Cl(-) flux data was consistent with that determined by the method of electrotonic spread for other marine crustacean muscle fibres. Cl(-) accounted for most of the membrane conductance.

Animals↗

Electrical activity observed in guinea-pig olfactory cortex maintained in vitro.

1. Electrical recordings were made from a preparation of guinea-pig olfactory cortex maintained in vitro.2. The response of the prepiriform area to a volley delivered to the lateral olfactory tract comprised a sharp negative deflexion upon which several positive notches were superimposed followed by a long-duration low-amplitude positive wave.3. Both the negative and positive waves were of maximal amplitude near the top surface of the preparation (the original cortical surface).4. Units recorded at depths of 250-350 mu showed facilitation and latency variation. The latency distribution of these spikes was very similar to that of the positive notches observed on the surface of the slice.5. The surface observed negative waves were rapidly abolished by oxygen lack.6. The negative and positive waves have been tentatively identified as the extracellular manifestations of the excitatory post-synaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs) occurring in the apical dendrites.7. Some spontaneous activity was observed in a proportion of the preparations studied.8. The evidence presented here strongly supports the contention that portions of the mammalian brain may be maintained in a satisfactory functional condition when isolated from the body, provided that they are maintained in a suitable environment. We believe that such preparations will prove very useful for physiological studies of the mammalian brain.

Action Potentials↗

Degenerate perturbations of protein structure as the mechanism of anaesthetic action.

The interaction of the n-alkanols with lipid bilayers and excitable membranes shows that there is no simple correlation between conduction block and any of the perturbations of bilayer structure currently proposed as unitary mechanisms of local anaesthetic action. We propose instead that the n-alkanols act by direct interaction with target proteins to cause perturbations which depend directly on the precise structure of the alcohol.

Alcohols↗

Modulation of the anchorage-independent phenotype of human lung fibroblasts obtained from fibrotic tissue following culture with retinoid and corticosteroid.

Fibroblast heterogeneity has been documented in fibrotic tissue from lung and skin. Differences have been demonstrated in proliferative rates in fibroblasts derived from fibrotic lung tissue as compared to normal. Fibroblast lines derived from adult fibrotic lung tissue and neonatal normal lung tissue exhibit colony growth in soft agarose culture, whereas fibroblast cell lines from normal adult lung tissue do not. The characteristic of anchorage-independent growth is consistent with the aggressive nature of the disease and with developmental lung growth. In this study, fibrotic lung fibroblasts were exposed to growth and differentiating factors to determine whether the anchorage-independent phenotype can be modulated. The results indicate that treatment of fibrotic lung fibroblasts with retinoic acid, known to modify matrix gene expression and induce differentiation, inhibits the cells ability to form colonies under soft agarose growth. Treatment with all-trans-retinoic acid yielded the greatest effect inhibiting both IPF and neonatal lung fibroblast anchorage-independent growth approximately 90% at 10(-6) M. Treatment of IPF fibroblasts with all-trans-retinoic acid also inhibited corticosteroid-induced colony growth. Modulation of the "fibrotic" fibroblast phenotype through retinoid therapy may prove beneficial as a potential therapeutic strategy.

Adrenal Cortex Hormones↗