PubMed Health⌕ Search

Biomedical subjects

A Mosfeldt Laursen

Publications and source records attributed to A Mosfeldt Laursen.

4 recordsLinked to original sources
PubMed1990

The effect of two lipophilic gamma-aminobutyric acid uptake blockers in CA1 of the rat hippocampal slice.

1. Drugs that increase inhibitory synaptic transmission in the central nervous system may be valuable tools in the treatment of seizures. Theoretically, substances that block the uptake of inhibitory transmitters such as gamma-aminobutyric acid (GABA) into intracellular compartments should also increase inhibition and therefore have potential value as antiepileptic drugs. However, most of these substances penetrate the blood-brain barrier poorly and have therefore until now had limited value. NO-05-0328 and NO-05-0329 are two new lipophilic GABA uptake inhibitors that readily enter the CNS from the blood. 2. We have investigated the effect of these two uptake inhibitors on the responses to exogenous GABA and on GABA-mediated inhibitory synaptic potentials in pyramidal neurones of the CA1 region in the rat hippocampal slice. 3. We found that both drugs increased the amplitude and duration of responses to exogenous GABA. Furthermore, the inhibitory synaptic potentials increased in amplitude. This increase was seen in both early and late phases of the synaptic potentials. We conclude that NO-05-0328 and NO-05-0329, at least in vitro, are more effective than older GABA uptake inhibitors such as nipecotic acid and they therefore deserve consideration for clinical use.

Animals↗
PubMed1989

Electrophysiological properties of hypoglossal motoneurons of guinea-pigs studied in vitro.

Intracellular recordings were made from the hypoglossal nuclear complex in brain slices from guinea-pigs. Retrograde transport of horseradish peroxidase from the tongue confirmed the identity of the visually identified hypoglossal nucleus. Eighteen neurons were stained by intracellular electrophoresis of Lucifer Yellow through the recording pipette. Two types of neurons were encountered, motoneurons with maximal discharge rates of 90 Hz and another type with maximal discharge rates of 250 Hz. Motoneurons were prevalent in the hypoglossal nucleus and the other type prevailed in the adjoining nucleus prepositus hypoglossi. In both nuclei the two types were mixed. Antidromic spikes elicited from hypoglossal root fibres had initial segment and somatodendritic components. Electrical stimulation of the reticular matter dorsolateral to the hypoglossal nucleus elicited excitatory postsynaptic potentials and strychnine sensitive inhibitory postsynaptic potentials. Motoneurons responded to depolarizing current pulses with a train of spikes. The initial spike interval was much shorter than the rest and fast adaptation occurred over three to four intervals. Slow adaptation was most prominent when the neuron was depolarized and discharged at a high rate. High threshold calcium spikes were evoked by depolarizing pulses when sodium spikes were blocked by tetrodotoxin and the potassium conductance reduced by tetraethylammonium bromide. Motoneurons discharged in a single range, inflections on the frequency-current plot being absent. Spikes and spike trains evoked by depolarizing pulses were followed by afterhyperpolarizations with fast and slow parts. The fast phase was eliminated by tetraethylammonium bromide, possibly because the delayed rectifier was involved. A calcium dependent potassium conductance was probably involved in the slow phase, because it was sensitive to inorganic calcium blockers. The amplitude of the afterhyperpolarization following trains of spikes depended on the frequency of the preceding spikes. At constant frequency, the amplitude depended, in addition, on the strength of stimuli arising from different hyperpolarized potentials. Afterdepolarizing potentials were absent. Lissajous plots of double ramp current stimulation showed anomalous rectification between resting potential and spike threshold. The rectification was sensitive to inorganic calcium blockers. Subthreshold responses showed initial sags and rebound responses in all healthy cells and these were eliminated by caesium. Barium, substituted for calcium, unleashed a depolarizing plateau potential sensitive to tetrodotoxin, indicating the presence of a persistent sodium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1984

The contribution of in vitro studies to the understanding of epilepsy.

The slice technique has turned out to be a valuable tool in the study of fundamental epileptic processes. Intracellular recording from brain tissue in vitro may be maintained for hours. The effect of changes in the perfusion medium may be studied easily without interference from the blood-brain barrier and tissue from different brain regions may be studied in isolation. Generally, brain cells in slices behave as brain cells in vivo in spite of the obvious possibilities for distorted metabolism. The cellular basis of the epileptic process is believed to be large depolarizing potentials. Although similar potentials recorded from cells in slices have been shown to be synaptic potentials, abnormal membrane properties are also induced by epileptogenic substances. The spread of the epileptic process may occur by direct electrical coupling via gap junctions, by local increases in extracellular potassium concentration or by synaptic transmission. Reduced GABA'ergic inhibition, account, at least in part, for epileptic discharges induced by epileptogenic drugs. The role for this mechanism in naturally occurring epilepsy is unknown, but it is probably involved somehow. GABA increases the conductance of the neuronal membrane to Cl. In hippocampal dendrites, it probably in addition increases the conductance to Na because here the induced inhibitory response is depolarizing. The somatic and dendritic membranes are also different in their excitatory responses. In the hippocampus, calcium spikes predominate in the dendrites whereas steady discharges consisting of sodium spikes are characteristic of the soma. The same receptor complex seems to be involved in dendrites and soma in the enhancing effect of benzodiazepines on GABA responses. However, GABA-benzodiazepine receptor complexes in other parts of the brain are probably constituted in different ways. We know of many disturbances in the brain which may be involved in epilepsy. A single critical deviation from normal physiology in naturally occurring epilepsy has not been identified. Possibly, the process may be initiated by any one of several factors, which all take part when the disease is established.

Animals↗