Modulation of transmission in different electronic junctions by aminopyridine

Summary 4 distinct electronic inputs can be identified in amphibian motoneurons perfused with calcium-free solution containing manganese. The differential effect of 4-aminopyridine on different electrotonic junctions may reflect the peculiarities of molecular architecture of potassium channels in different electrically excitable presynaptic membranes.We thank Prof. D. R. Curtis, of National University Canberra, for the gift of 4-aminopyridine.     

Zentrale Wirkung des Cholinesterasehemmers Pyridostigmin

Summary By injection of cholinesterase-inhibitor and vagotonic pyridostigmine into thecisterna cerebello-medullaris in dogs, it is possible to evoke a state of psychomotoric excitement resembling that seen in various human diseases. On the other hand, intracisternally injected epinephrine (central anesthesia) and pyridostigmine each inhibit the other's action.     

Selective blockade of components of potassium activation in Myxicola axons

The K+ conductance in Myxicola giant axons activates in two phases which are pharmacologically separable. The fast phase of K+ activation is specifically inhibited by 4-aminopyridine and by the substitution of D2O for H2O. We suggest Myxicola giant axons, like the amphibian node of Ranvier, may possess more than one variety of K+ channel.     

Modulation of transmission in different electronic junctions by aminopyridine.

4 distinct electronic inputs can be identified in amphibian motoneurons perfused with calcium-free solution containing manganese. The differential effect of 4-aminopyridine on different electronic junctions may reflect the peculiarities of molecular architecture of potassium channels in different electrically excitable presynaptic membranes.     

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

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.     

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".     

Excitation-contraction coupling in the myocardium of hibernating chipmunks

In the myocardium of nonhibernating chipmunks, replacing external Ca by Sr markedly prolongs the action potential plateau with an increase in contraction, while in preparations from hibernating animals this procedure inhibits both responses. Pretreatment with 4-aminopyridine causes a prolongation of the action potential plateau by Sr in hibernating animals.     

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)....     

Selective blockade of components of potassium activation inMyxicola axons

Summary The K⁺ conductance inMyxicola giant axons activates in two phases which are pharmacologically separable. The fast phase of K⁺ activation is specifically inhibited by 4-aminopyridine and by the substitution of D₂O for H₂O. We suggestMyxicola giant axons, like the amphibian node of Ranvier, may possess more than one variety of K⁺ channel.     

Changes in transmitter release at frog neuromuscular junction induced by 4-aminopyridine]

4-aminopyridine (4-AP) at micromolar concentrations, increases the end-plate potential amplitude in curarized preparations and the mean quantal content in every preparation tested, but the spontaneous release is not modified by 4-AP. These results can explain the anticurare activity observed in the wole animal or in vitro. 4-AP prolongs the falling phase of the muscle action potential without change in the muscle membrane potential.     

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.     

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).     

Comparative effects of ouabain, natriuretic factor and ammonium chloride in the toad urinary bladder

Electrical changes and direct effects on Na-K ATPase activity induced by an endogenous digitalis-like natriuretic factor (NF), NH4Cl and ouabain were studied in toad bladders. NF inhibited the SCC and the Na-K ATPase activity in a similar manner to ouabain, but induced a greater increase in calculated direct current resistance (R) (p less than 0.05). NH4Cl was a weak inhibitor of Na-K ATPase activity, although it produced steeper SCC inhibition slopes than those observed with ouabain or NF (p less than 0.01). The data suggested the same mechanism of action of NF and ouabain on the sodium pump, with an additional effect of the former on apical sodium permeability of the cells and/or closure of paracellular routes leading to an increased tissue resistance. In contrast, the effects of NH4Cl were mostly compatible with intracellular inhibition of apical sodium entry into the cell.     

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.     

D-ala2-Metenkephalinamide blocks the synaptically elicited cortical spreading depression in rats

Spreading depression (SD) was elicited in rats anesthetized with pentobarbital by a train of 8 electrical pulses (0.1 ms, 10 Hz) applied to parietal cortex. Local application of 50 micrograms of D-ala2-metenkephalinamide (DAME) on the stimulated area evoked one or two SD waves followed by an increase of SD threshold from 40 V to 90 V. This effect could be partly prevented by naloxone (1 mg/kg i.p.) and reversed by local application of 4-aminopyridine (10(-3) M, 2 microliters), which reduced SD threshold to 5 and 20 V in normal and DAME-treated cortex, respectively. It is argued that DAME exerts an inhibitory effect on cortical neurons and that the initial SD facilitation is due to initial blockade of inhibitory neurons in the superficial cortical layers.     

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.     

Über eine Tetrahydroisochinolinverbindung mit analgetischer Wirkung

Summary Ro 4-1778/1 (1-(p-Chlorphenethyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) showed in pharmacological tests distinct analgetic effects similar to those of codeine as well as some spasmolytic activity resembling that of papaverine, whereas its side effects were absent or at least considerably less pronounced than those known for codeine.     

Pentobarbital: Presynaptic effect in the squid giant synapse

Summary In concentrations that produced synaptic blockade in the squid giant synapse, sodium pentobarbital produced a dose-related, reversible decrease of the calcium spike of the presynaptic terminal.This work was performed while Dr Morgan was a Grass Foundation Fellow at the Marine Biological Laboratory, Woods Hole, Massachusetts, USA.The authors thank Dr J. Z. Yeh for the loan of the 4-aminopyridine and Dr G. H. Acheson for helpful suggestions.     

Stimulation of the growth of murine bone marrow colonies in vitro by an acute inflammatory exudate. Comparison with colony stimulating factor CSF)]

Formation of colonies from mice bone marrow progenitors of macrophages and granulocytes in methylcellulose culture was induced by an inflammatory pleural exudate obtained from mice injected with dextran. Mitogenic activity of this acute inflammatory exudate was compared with that of colony stimulating factor (CSF). It was found that colony and cluster counts, during 10 days of culture, were similar with the two types of stimulating factors. When used at the same dose, exudate was less active than CSF. It was concluded that inflammatory exudate showed an activity similar to that of CSF but contained a smaller amount of stimulating factor. Further cytochemical studies are necessary to specify whether or not the two factors induced the same type of colonies (monocytic or granulocytic).     

Mechanical and biochemical characterization of the contraction elicited by a calcium-independent myosin light chain kinase in chemically skinned smooth muscle

The contraction induced by a Ca2+-independent myosin light chain kinase (MLCK-) was characterized in terms of isometric force (Fo), immediate elastic recoil (SE), unloaded shortening velocity (Vus), shortening under a constant load and ATPase activity of chemically skinned smooth muscle preparations. These parameters were compared to those measured in a Ca2+ -induced contraction to assess the nature of cross bridge interaction in the MLCK-induced contraction. Fo developed in chicken gizzard fibers as well as SE were similar in contractions elicited by either agent. Vus in the contraction induced by MLCK-(0.36 mg/ml) was similar though averaged 39.3 +/- 8.9% less than Vus induced by Ca2+ (1.6 X 10(-6) M) in the control fibers. Addition of Ca2+ (1.6 X 10(-6) M) to a contraction induced by MLCK-resulted in small increases in both Fo and Vus. Shortening under a constant load was similar for both types of contractions. The contraction induced by MLCK-was accompanied by an increased rate of ATP hydrolysis. The MLCK-induced contraction is thus kinetically similar though not identical to a contraction induced by Ca2+. We conclude that with respect to actin-myosin interaction, MLCK-and Ca2+ -induced contractions are similar.