4-Aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices

Summary The exact mode of action of the anti-epileptic agent carbamazepine is unknown. In hippocampal slices in which epileptiform discharges were induced by addition of penicillin to the perfusion medium, the depressant effect of carbamazepine was attenuated by the potassium-channel blockers barium chloride (0.1 mM) and 4-aminopyridine (200 M), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.     

4-Aminopyridine and fiber potentials in rat and human hippocampal slices

Cellular and Molecular Life Sciences - Compound fiber action potentials of stratum radiatum afferents in slices from human and rat hippocampus are shown to be prolonged by 4-aminopyridine (4-AP)....     

Voltage-clamp analysis of the sodium and potassium currents in skeletal muscle fibres treated with 4-aminopyridine

Summary External application of low concentrations of 4-aminopyridine blocks potassium currents without affecting sodium currents in pieces of single frog skeletal muscle fibres. The blockade of potassium currents was voltage-dependent, being partially relieved on depolarization.This study was supported by a grant from the Oficina técnica de Desarrollo Cientifico of the University of Chile (Project 4437-R, 1977).     

Model of the effect of 4-aminopyridine at the level of potassium channels of the giant axon of the squid, Logigo forbesi L.]

Most of the effects of 4-aminopyridine on the potassium conductance of the giant axon of the Squid can be explained in terms of a simple model based on the physicochemical properties of the molecule and what is known about the structure of the potassium "channels".     

Differential sensitivity of amphibian nodal and paranodal K+ channels to 4-aminopyridine and TEA

Voltage-dependent K+ channels are blocked by several drugs, including 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP is most widely used to localize K+ channels in mammalian and non-mammalian nerve fibers, but 4-AP and TEA alter various K+ channels and/or preparations in specific ways. The reason is not known, in part because dissociation constants for 4-AP and TEA have not been measured for nodal and internodal K+ channels in the same fibers. Smith and Schauf showed that the density of nodal versus paranodal K+ channels in frog nerves depends on fiber diameter. The size dependence was used to determine the relative sensitivity of nodal and internodal K+ channels to 4-AP and TEA, and to compare voltage- and time-dependent activation. The results show nodal and internodal K+ channels activate similarly. However, internodal channels are selectivity blocked by 4-AP while TEA is more effective on nodal channels. A high sensitivity of internodal K+ channels may explain why 4-AP improves symptoms in diseases such as multiple sclerosis.     

Differential sensitivity of amphibian nodal and paranodal K+ channels to 4-aminopyridine and TEA

Summary Voltage-dependent K⁺ channels are blocked by several drugs, including 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP is most widely used to localize K⁺ channels in mammalian and non-mammalian nerve fibers, but 4-AP and TEA alter various K⁺ channels and/or preparations in specific ways. The reason is not known, in part because dissociation constants for 4-AP and TEA have not been measured for nodal and internodal K⁺ channels in the same fibers. Smith and Schauf showed that the density of nodal versus paranodal K⁺ channels in frog nerves depends on fiber diameter. This size dependence was used to determine the relative sensitivity of nodal and internodal K⁺ channels to 4-AP and TEA, and to compare voltage- and time-dependent activation. The results show nodal and internodal K⁺ channels activate similarly. However, internodal channels are selectivity blocked by 4-AP while TEA is more effective on nodal channels. A high sensitivity of internodal K⁺ channels may explain why 4-AP improves symptoms in diseases such as multiple sclerosis.     

Sympatho-inhibitory mechanisms acting at sympathetic ganglia to attenuate hypothalamic-induced pressor effect in the cat

Summary Pressor and tachycardic effects induced in the cat by stimulation of a lateral hypothalamic (LH) site, are shown to be mediated by sympathetic ganglia nicotinic receptor, and potentiated under atropine methyl nitrate sympathetic ganglia blockage. It is postulated that a sympatho-inhibitory pathway muscarinic ganglionic mechanism, co-activated by the LH stimulation, attenuates the pressor and tachycardic effects, the potentiation presumably being a manifestation of blockage of that mechanism.     

Sympatho-inhibitory mechanisms acting at sympathetic ganglia to attenuate hypothalamic-induced pressor effect in the cat

Pressor and tachycardic effects induced in the cat by stimulation of a lateral hypothalamic (LH) site, are shown to be mediated by sympathetic ganglia nicotinic receptor, and potentiated under atropine methyl nitrate sympathetic ganglia blockage. It is postulated that a sympatho-inhibitory pathway muscarinic ganglionic mechanism, co-activated by the LH stimulation, attenuates the pressor and tachycardic effects, the potentiation presumably being a manifestation of blockage of that mechanism.     

Effects of glycolytic metabolites on preservation of high energy phosphate level and synaptic transmission in the granule cells of guinea pig hippocampal slices

The present study was undertaken to investigate whether neural activity of hippocampal slices can be preserved after replacingd-glucose with glycolytic intermediate metabolites such as lactate, pyruvate and citrate or with other sugars such as fructose, mannose, maltose, glucosamine, sucrose and galactose. As an index of neural activity, population spikes (PS) were recorded in the granule cell layers after electrical stimulation to the perforant path of guinea pig hippocampal slices. In addition, we determined the levels of ATP and creatine phosphate (CrP) in each slice after the replacement ofd-glucose with these substrates, and correlated it with the neural activity. Substrates other thand-glucose could not maintain the PS for even 20 min although the slices perfused with medium containing lactate, pyruvate, galactose, fructose and maltose maintained similar levels of ATP and CrP as in slices incubated in thed-glucose-containing medium. These results indicate thatd-glucose is essential for the preservation of synaptic activity in addition to its main role as the substrate for energy production to maintain the levels of high energy phosphates.     

The effect of 5-hydroxytryptophan on the efflux of noradrenaline from brain slices

Zusammenfassung 5-Hydroxytryptophan erniedrigt die Konzentration von Noradrenalin in Hirnschnitten, sofern diese das Amin zuvor aus zugesetzteml-DOPA selber synthetisierten. Dieser Effekt beruht vermutlich darauf, dass 5-Hydroxytryptophan die Decaroxylierung desl-DOPA, das im Hirngewebe gespeichert wird, kompetitiv hemmt. Die Relation der Noradrenalin- und Serotoninkonzentration im Hirngewebe kann somit auch durch ein verändertes Angebot an Aminosäuren gestört werden.     

Possible explanation for interictal-ictal transition: Evolution of epileptiform activity,in hippocampal slice by chloride depletion

Summary In thin hippocampal slices, paroxysmal epileptiform discharge was generated in high potassium medium. Removal of chloride from the high potassium medium caused explosive potentiation of the paroxysmal discharge and emergence of clonic relapsing discharges. Evolution of the paroxysm to regenerative seizure was attributed to the reduction of inhibitory postsynaptic potentials.     

The effect of nickel chloride on the permeability of the blood-brain barrier

Zusammenfassung Die Permeabilitätsverhältnisse der Blut-Hirn-Schranke nach spezifischer Hemmung der 5-Nucleosid-Phosphatase wurden mittels Fluoreszenzmikroskopie studiert und eine Permeabilitätserhöhung nach Injektion von Nickelchlorid gefunden: Trypanblau kann dabei ins Gehirn penetrieren, was dafür spricht, dass die 5-Nucleosid-Phosphatase bei der Regulation der Kapillarpermeabilität eine bedeutende Rolle spielt.     

Possible explanation for interictal-ictal transition: evolution of epileptiform activity in hippocampal slice by chloride depletion.

In thin hippocampal slices, paroxysmal epileptiform discharge was generated in high potassium medium. Removal of chloride from the high potassium medium caused explosive potentiation of the paroxysmal discharge and emergence of clonic relapsing discharges. Evolution of the paroxysm to regenerative seizure was attributed to the reduction of inhibitory postsynaptic potentials.     

An assessment of the effect of hormone and neurotransmitters on adenine and gluanine derivatives simultaneously in rat brain cortical slices

Summary A 2-dimensional thin-layer method has been developed for the separation on cellulose of adenine and guanine derivatives. Using incubated rat cerebral cortex slices it was shown that noradrenaline and acetylcholine stirnulated cAMP and cGMP production respectively but glutamate and -aminobutyric acid stimulated production of both cyclic nucleotides.     

An assessment of the effect of hormone and neurotransmitters on adenine and guanine derivatives simultaneously in rat brain cortical slices.

A A 2-dimensional thin-layer method has been developed for the separation on cellulose of adenine and guanine derivatives. Using incubated rat cerebral cortex slices it was shown that noradrenaline and acetylcholine stimulated cAMP and cGMP production respectively but glutamate and gamma-aminobutyric acid stimulated production of both cyclic nucleotides.     

The influence of antistine on glycogenolytic effect of some biogenic amines in rat brain slices

Résumé On a démontré que l'antistine empêche in vitro l'effet glycogénolytique de l'histamine, bien qu'elle n'ait pas d'influence sur les actions glycogénolytiques de la noradrénaline, de la dopamine, de la sérotonine, du 3, 5-AMP cyclique et de son dérivé dibutirique. Ces résultats suggèrent l'existence de récepteurs particuliers pour les amines biogénique dans le tissue du cortex, du nucleus caudatus et du thalamus. De ces résultats on a conclu que, dans le cerveau du rat, l'adénocyclase pourrait être le récepteur histaminique.