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Biomedical subjects

D A Prince

Publications and source records attributed to D A Prince.

At least 145 records · Page 8Linked to original sources
PubMed1977

Presynaptic origin of penicillin after discharges at mammalian nerve terminals.

The site of origin and mechanism underlying the generation of repetitive after-discharges produced by penicillin was studied in the isolated rat phrenic nerve-hemidiaphragm preparation. Application of low concentrations of sodium penicillin to the bathing solution initiated bursts of antidromic action potentials originating at or near the motor nerve terminals following single orthodromic stimuli to the nerve. Afterdischarges could not be elicited by direct stimulation of the muscle fibers alone, or when the nerve trunk was isolated from the neuromuscular junction and exposed to penicillin. D-Tubocurarine applied in doses sufficient to abolish postsynaptic responses did not diminish penicillin-induced after discharges. At concentrations which most reliably produced repetitive firing (5000 IU/ml; 8.5 mM), penicillin did not accelerate the frequency of spontaneous transmitter release (MEPPs), yet significantly increased the relative excitability of nerve endings to extracellular stimulation. It is concluded that penicillin acts directly and preferentially on presynaptic nerve terminals to induce repetitive afterdischarges which arise independently of postsynaptic depolarization, transmitter-mediated potassium efflux, or muscle fiber contraction. The results suggest that the convulsant effects of penicillin at a mammalian neuromuscular junction are due to non-depolarizing alterations in the intrinsic excitability of the terminal membrane which increase the probability of suprathreshold depolarizations during the recovery period of spike electrogenesis. Several models of the mechanisms which might produce hyperexcitability at presynaptic nerve terminals are discussed.

Animals↗
PubMed1977

Penicillin-induced epileptiform activity in the hippocampal in vitro prepatation.

An in vitro preparation has been developed in which epileptogenesis in mammalian central nervous system tissue may be studied. Addition of sodium penicillin to the medium bathing slices of guinea pig hippocampus induced epileptiform activity similar to that seen in hippocampal penicillin foci in vivo. Epileptiform events were recorded as synchronous field potentials and correlated cellular bursts that occurred spontaneously and could be triggered by orthodromic stimulation. Intracellular recordings revealed that bursts were generated from large depolarization shifts in some neurons, while in others, burst discharges had little underlying baseline depolarization. This finding, and the presence of fast prepotentials in penicillin-treated preparations, suggested the involvement of dendritic activity in generation of epileptiform discharges.

Animals↗
PubMed1977

Spike-wave rhythms in cat cortex induced by parenteral penicillin. I. Electroencephalographic features.

Surface and depth recordings were made in 21 cats with generalized, parenteral penicillin induced epileptiform activity often assuming spike-wave forms, to obtain information on the structural substrate of "spontaneous" spike-wave rhythms. Recordings were made from neocortex, medial and lateral thalamus, hippocampus and brainstem reticular formation. Epileptiform activity first appeared in cortex and subsequently projected to depth structures. Occasionally, focal discharges could be seen in subcortical structures, but these generally did not spread to cortex. No consistent "pacemaker" was identified in cortex or depth. Bilateral applications of penicillin to cortex produced synchronous spike-wave bursts. In contrast, ventriculocisternal perfusion of penicillin solutions yielded synchronous cortical potentials which differed clearly in morphology and frequency from parenterally induced spike-wave bursts. During generalized activity, transcortical, intrahemispheric lesions interfered with ipsilateral synchrony. After transcortical section, projection of localized cortical bursts to thalamus did not necessarily result in "recruitment" of diffuse cortical regions into epileptiform activity. These results emphasize the importance of cortical circuitry and corticocortical connections in the genesis and synchronization of spike-wave rhythms.

Animals↗
PubMed1977

Spike-wave rhythms in cat cortex induced by parenteral penicillin. II. Cellular features.

Epileptiform potentials, consisting of spontaneous, generalized bursts frequently assuming a 3/sec spike-wave form and tonic clonic electrographic seizures were produced in 32 lightly anesthetized cats by parenteral injections of penicillin. The activity of 83 identified pyramidal tract cells and 207 cortical non-pyramidal tract cells was correlated with the surface EEG. The majority of both cell types generated depolarizations and action potentials with the EEG spike. Hyperpolarizations, during which cells were inhibited, followed the depolarizations. The depolarizations responded to injected current as if they were generated by excitatory synapses; and hyperpolarizations to injected current and chloride ions as if generated by proximal inhibitory synapses. Attempts to identify a class of neurons firing during the surface-negative wave (presumed inhibitory interneurons) were unsuccessful. Forty-two units were recorded during tonic-clonic seizures. Intracellular records disclosed tonic oscillations of membrane potential, phased bursting with "depolarization shifts", abortive action potentials and post-ictal hyperpolarizations. Cell somata often depolarized to the point of inactivation, but axons continued to fire at high rates. These results emphasize the role of EPSP-IPSP sequences in the generation of spike-wave rhythms.

Action Potentials↗
PubMed1976

Regulation of extracellular potassium concentration in epileptogenesis.

Characteristic elevations in the brain's extracellular potassium concentration [K+]0 occur during focal epileptogenesis. These changes have particular spatial and temporal profiles that are different in hippocampus and neocortex, and in mature and immature animals. Increases in [K+]0 cannot be the sole explanation for regional variations in seizure susceptibility, interictal-ictal transitions, or termination of ictal episodes. Excess [K+]0 is cleared primarily by passive diffusion with a small amount taken up into cells and blood vessels. Cortical neuroglia have sensitivities to changes in [K+]0 similar to that observed in glial cells in invertebrates and amphibia. However, discrepancies in the expected relationship between [K+]o and glial membrane potential Vm suggest either a heterogeneous population of glial cell types and/or the presence of a glial syncytium which acts as a spatial buffer to increases in [K+]0.

Animals↗
PubMed1976

Kinetics of potassium movement in norman cortex.

Artificial CSF containing 12mEq/1 of potassium (4 times normal concentration) was perfused over the surface of normal neocortex in 10 locally or barbiturate anesthetized cats. Extracellular potassium concentrations ([K+]OS) were measured as a function of time to 8 h and of depth to 3 mm. Analysis of the [K+]O versus depth and [K+]O versus time profiles showed that the distribution of extracellular potassium could be modelled by a process of diffusion with diffusion coefficient = 1.03 +/- 0.16 sq.mm/h, and a surface barrier to diffusion with magnitude given by a barrier constant 0.8 +/- 0.2 mm-1, and with a small correction for active uptake into cells and blood vessels. The profiles obtained differ considerably from those which could be predicted from kinetic properties of potassium in aqueous solution.

Anesthesia, General↗
PubMed1976

The role of extracellular potassium in hippocampal epilepsy.

It has been proposed that the notable capacity for epileptogenesis in the hippocampus may be related to potassium accumulation in extracellular spaces. To investigate this hypothesis more directly, we measured changes in extracellular potassium concentration ([K+]o) during focal hippocampal epilepsy using potassium-sensitive microelectrodes. Interictal and ictal electroencephalographic events were accompanied by increases in [K+]o that varied systematically with depth from the ependymal surface and lateral distance from the focus. Maximal [K+]o changes during interictal and ictal discharges occurred in the stratum pyramidale. Initiation of ictal activity did not correlate with a particular "threshold" [K+]o. Comparing these results with similar data from neocortex, we observed that interictal K+ responses in hippocampus lasted longer and had slower rise times, and that peak interictal and ictal [K+]o values were consistently lower. Increases in [K+]o cannot be the sole explanation for regional variations in seizure susceptibility, interictal-ictal transitions, or termination of ictal episodes.

Animals↗
PubMed1975

Effect of penicillin on an excitatory synapse.

When penicillin, an epileptogenic agent, was applied to the neuromuscular junctions of the superficial flexor muscles of crayfish, the excitatory junctional potential (EJP) amplitudes were increased by 50-200%. This effect of the drug was not due to changes in the passive electrical properties of the muscle cell membrane or to an increase in its chemical sensitivity to acetylcholine (ACh), the presumed transmitter at the junction studied. Inactivating the penicillin with the enzyme penicillinase, or substituting acetate for penicillin in the test solutions eliminated the effect on EJPs, showing that the penicillin ion was the active agent. Penicillin ions did decrease the frequency of spontaneous miniature EJPs and increase the amplitude or presynaptic spikes recorded extracellularly, suggesting that augmentation of EJPs may have been due to alterations at the presynaptic nerve terminals.

Acetylcholine↗
PubMed1975

Transcallosal effects of a cortical epileptiform focus.

Unit activity in anesthetized cats was studied in cortical regions contralateral to the site of an acute epileptiform focus. Orthodromic effects of transcallosal discharge varied in extracellular records; however, in intracellular records, most cells displayed an EPSP-IPSP sequence. In a small proportion of cells, antidromic activation was also observed. The significance of this 'backfiring' phenomenon, and some factors possibly involved in generation of 'backfiring' activity, are discussed.

Animals↗