Search results for "4-Aminopyridine"
showing 10 items of 24 documents
Five years experience on 3,4-diaminopyridine phosphate in Lambert-Eaton syndrome: Case reports
2017
Abstract Rationale: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert–Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. Patient concerns: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (…
Cognitive deficits in aged rats correlate with levels of l-arginine, not with nNOS expression or 3,4-DAP-evoked transmitter release in the frontopari…
2005
Aging is associated with altered neurotransmitter function in the brain. In this study, we measured release parameters for acetylcholine (ACh), norepinephrine and serotonin in the frontoparietal cortex of young and aged rats. We also determined cortical amino acid concentrations and nitric oxide (NO) synthase function. Prior to sacrifice, the rats had been tested for Morris water-maze performance. In aged, compared with young rats, we observed a reduction in both uptake of choline and acetylcholine release. Serotonin release and L-arginine concentrations (a precursor of NO) showed an aging-related increase; however, L-citrulline/L-arginine ratios were decreased in aged rats. Moreover, while…
Subventricular zone neural progenitors protect striatal neurons from glutamatergic excitotoxicity.
2012
The functional significance of adult neural stem and progenitor cells in hippocampal-dependent learning and memory has been well documented. Although adult neural stem and progenitor cells in the subventricular zone are known to migrate to, maintain and reorganize the olfactory bulb, it is less clear whether they are functionally required for other processes. Using a conditional transgenic mouse model, selective ablation of adult neural stem and progenitor cells in the subventricular zone induced a dramatic increase in morbidity and mortality of central nervous system disorders characterized by excitotoxicity-induced cell death accompanied by reactive inflammation, such as 4-aminopyridine-i…
Generalization of seizures parallels the formation of "dark" neurons in the hippocampus and pontine reticular formation after focal-cortical applicat…
2008
Abstract Distribution and time course of the occurrence of “dark” neurons were compared with the EEG activity and behavior of rats during 4-aminopyridine (4-AP) induced epileptic seizures. A crystal of the K + channel blocker 4-AP (0.5 mg/kg) was placed onto the exposed parieto-occipital cortex of Halothane-anesthetized rats for 40 min. Thereafter, the anesthesia was discontinued and the behavioral signs of the epileptic seizure activity were observed. The presence of “dark” neurons was demonstrated by the sensitive silver method of Gallyas in rats sacrificed at 0, 3 and 6 h after the end of the 4-AP crystal application. The EEG activity was recorded in the rats with longer survival times. …
Pathology-selective antiepileptic effects in the focal freeze-lesion rat model of malformation of cortical development
2021
Malformations of cortical development (MCD) represent a group of rare diseases with severe clinical presentation as epileptic and pharmacoresistant encephalopathies. Morphological studies in tissue from MCD patients have revealed reduced GABAergic efficacy and increased intracellular chloride concentration in neuronal cells as important pathophysiological mechanisms in MCD. Also, in various animal models, alterations of GABAergic inhibition have been postulated as a predominant factor contributing to perilesional hyperexcitability. Along with this line, the NKCC1 inhibitor bumetanide has been postulated as a potential drug for treatment of epilepsy, mediating its antiepileptic effect by red…
4-Aminopyridine antagonizes the inhibitory effect of pentobarbital on acetylcholine release in the heart
1980
Effects of pentobarbital on acetylcholine (ACh) release, force of contraction and nervous conduction were studied in isolated heart preparations and in cervical vagus nerves, respectively. 4-Aminopyridine and tetracaine were used as pharmacological tools to eludicate the mode of action of pentobarbital. 1. 4-Aminopyridine (10−4 M) markedly increased the overflow of ACh from the isolated chicken heart evoked by electrical stimulation (1–50 Hz, 1 ms, 40 V) of the cervical vagus nerves. This effect of 4-aminopyridine was highest at low frequencies of stimulation (+ 226% at 1 Hz) and declined with increasing frequencies to reach a minimum augmentation of 22% at 30 Hz. 2. Pentobarbital and tetra…
Inhibition of different GABA transporter systems is required to attenuate epileptiform activity in the CA3 region of the immature rat hippocampus
2014
GABA transporters (GATs) are an essential element of the GABAergic system, which regulate excitability in the central nervous system and are thus used as targets for anticonvulsive therapy. However, in the immature nervous system the functions of the GABAergic system and the expression profile of GATs are distinct from the adult situation, obscuring to predict how different GAT isoforms influence epileptiform activity. Therefore we analyzed the effects of subtype specific GAT inhibitors on repetitive epileptiform discharges using field potential and whole-cell patch-clamp recordings in the CA3 region of hippocampal slices of immature (postnatal days 4-7) rats. These experiments revealed tha…
A homeostatic mechanism counteracting K+-evoked choline release in adult brain
2002
Choline (Ch) is an essential nutrient as the biosynthetic precursor of acetylcholine (ACh) and phospholipids. Under resting conditions, the intracellular accumulation of Ch (above 10-fold), which is positively charged, is governed by the membrane potential and follows the Nernst equation. Accordingly, in synaptosomes from adult rats during depolarization, we observed a linear relationship between release of free cytoplasmic Ch and KCl concentration (2.7-120 mm). The K(+) -evoked Ch release was Ca(2+) -independent and did not originate from ACh or phospholipid hydrolysis. In superfused brain slices of adult rats, however, a K(+) -induced Ch efflux was absent. Also, under in vivo conditions, …
Mechanism of Block by 4-Aminopyridine of the Transient Outward Current in Rat Ventricular Cardiomyocytes
1998
The effects of 4-aminopyridine (4-AP) on the transient outward current (I to ) were investigated in rat ventricular cardiomyocytes at different values of intracellular pH (pH i ) and extracellular pH (pH o ). The 4-AP was administered either extracellularly (bath application) or intracellularly (diffusion from the intrapipette solution). The 4-AP diminished I to given either from inside or outside the cell membrane. The block by extracellularly applied 4-AP (4-AP o ) of the peak amplitude of I to was decreased by external acidification but increased by external alkalinization: conversely. the block by 4-AP o was decreased by internal alkalinization but increased by internal acidification. I…
4-Aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices
1991
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 microM), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.