Effects of 4‐aminopyridine on Statistical Parameters of Transmitter Release at the Neuromuscular Junction

Lundh, Håkan

doi:10.1111/j.1600-0773.1979.tb02341.x

Cited by 23 publications

(2 citation statements)

References 24 publications

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“…2A, the increase in m caused by a 10-min incubation with 10 µM 3,4-DAP in 0.2 mM Ca 2+ solutions was due entirely to the apparently anomalous effect of an increase in the parameter n, with no measurable effect on the parameter p. Specifically, the value for m increased from 5.29 ± 0.46 in control to 10.43 ± 1.11 after 3,4-DAP (P < 0.005), the value for n increased from 13.4 ± 2.1 in control to 20.7 ± 1.8 after 3,4-DAP (P < 0.05), and the value for p was unchanged (0.45 ± 0.07 in control and 0.51 ± 0.07 after 3,4-DAP, n = 6 experiments from single endplates, separate preparations). This confirms the previous finding of Lundh (1979) using the related agent 4-aminopyridine.…”

Section: Independent Modulation Of the Binomial Parameter P In Sr 2+ supporting

confidence: 92%

Mechanisms of Neuromodulation as Dissected Using Sr²⁺ at Motor Nerve Endings

Searl

Silinsky²

2008

Journal of Neurophysiology

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The use of binomial analysis as a tool for determining the sites of action of neuromodulators may be complicated by the nonuniformity of release probability. One of the potential sources for nonuniformity of release probability is the presence of multiple forms of synaptotagmins, the Ca2+ sensors responsible for triggering vesicular exocytosis. In this study we have used Sr2+, an ion whose actions may be restricted to a subpopulation of synaptotagmins, in an attempt to obtain meaningful estimates of the binomial parameters p (the probability of evoked acetylcholine [Ach] release) and n (the immediate available store of ACh quanta, whereby m = np). In contrast to results in Ca2+ solutions, binomial analysis of Sr2+-dependent release reveals a dramatically reduced dependence of n on extracellular Sr2+ concentrations. In Sr2+ solutions, blockade of potassium channels with 3,4-diaminopyridine increased m by an exclusive increase in p, whereas treatment with phorbol ester increased m solely by effects on n. The cyclic adenosine monophosphate (cAMP) analogue CPT-cAMP increased m by increasing both n and p. The effect of CPT-cAMP on p but not on n was blocked by protein kinase A (PKA) inhibitors, whereas the effect on n was mimicked by 8-CPT-2'-O-Me-cAMP, a selective agonist for exchange protein directly activated by cAMP, otherwise known as the cAMP-sensitive guanine nucleotide-exchange protein. The results demonstrate both the utility of the binomial distribution in Sr2+ solutions and the dual effects of cyclic AMP on both PKA-dependent and PKA-independent processes at the amphibian neuromuscular junction.

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Section: Independent Modulation Of the Binomial Parameter P In Sr 2+ supporting

confidence: 92%

Mechanisms of Neuromodulation as Dissected Using Sr²⁺ at Motor Nerve Endings

Searl

Silinsky²

2008

Journal of Neurophysiology

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“…4-AP has been shown to facilitate excitation-contraction coupling in skeletal muscle (Kahn & Edman 1979). The effect of 4-AP on transmitter release is caused by an increase of the influx of calcium ions into the nerve terminal during depolarization (Lundh 1978) which probably enhances the number of active release sites for the transmitter (Lundh 1979). The effect of 4-AP on transmitter release is caused by an increase of the influx of calcium ions into the nerve terminal during depolarization (Lundh 1978) which probably enhances the number of active release sites for the transmitter (Lundh 1979).…”

Section: Discussionmentioning

confidence: 99%

Action of 4-aminopyridine on the cerebral circulation

Edvinsson

Hardebo

Lundh

2009

Acta Neurologica Scandinavica

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LUNDH4-Aminopyridine (4-AP) facilitates both inhibitory and excitatory synaptic activity in the central nervous system, and may, therefore, be a drug of potential therapeutic use in brain diseases with a disturbed synaptic transmission. In the present study the vasomotor effects upon isolated feline brain vessels, and regional cerebral blood flow and brain cortical metabolism in rats were examined. A t high concentrations (above 10-6M) a minor vasoconstriction was obtained of isolated pial vessels. Measurements of regional cerebral blood flow using the W-ethanol technique resulted in a significant increase in blood flow of caudate nucleus (93 %), thalamus (74 %) and cerebellum (82 %). The arteriovenous oxygen difference of cortical tissue was reduced from 3.20 mmol O d m l to 1.69 mmol O d m l by 4-AP. This was not associated with an increase in cortical blood flow. Calculation of the cortical metabolic rate of oxygen, however, failed to demonstrate any significant change.

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Effects of 4-Aminopyridine on Saxitoxin Intoxication

CHEN

Lin

WANG

1996

Toxicology and Applied Pharmacology

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Effects of 4-aminopyridine (4-AP) on neurotoxicity induced by saxitoxin (STX) are investigated in this study. In vitro, twitch tension evoked by nerve stimulation was depressed by STX (1.35 nM) in rat phrenic nerve-diaphragm preparations, and this inhibition was antagonized by 4-AP (0.1 mM). In addition, 4-AP (0.1 mM) restored the firing of membrane action potentials that were suppressed or even abolished by 0.334 nM STX in frog sartorius muscles. In vivo studies showed that 4-AP (0.3 mg/kg, iv) significantly reversed the respiratory rate, tidal volume, and blood pressure to normal values in anesthetized STX-toxicosis rats. Furthermore, 4-AP (0.75-6 mg/kg, ip) not only prolonged the survival time but also decreased the mortality of mice (71-43%) at a normally lethal dose (30 micrograms/kg, ip) of STX. The results suggest that 4-AP may be useful as an antidote for STX intoxication.

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Effects of 4‐aminopyridine on Statistical Parameters of Transmitter Release at the Neuromuscular Junction

Abstract: Abstrucc 4-Aminopyridine (CAP) potentiates transmitter release from motor nerve terminals by increasing the quantum content (m) of endplate potentials. Estimates of the binomial parameters of transmitter release shows that 4-AP enhances m by increasing n and not p.

Cited by 23 publications

References 24 publications

Mechanisms of Neuromodulation as Dissected Using Sr²⁺ at Motor Nerve Endings

Mechanisms of Neuromodulation as Dissected Using Sr²⁺ at Motor Nerve Endings

Action of 4-aminopyridine on the cerebral circulation

Effects of 4-Aminopyridine on Saxitoxin Intoxication

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Effects of 4‐aminopyridine on Statistical Parameters of Transmitter Release at the Neuromuscular Junction

Abstract: Abstrucc 4-Aminopyridine (CAP) potentiates transmitter release from motor nerve terminals by increasing the quantum content (m) of endplate potentials. Estimates of the binomial parameters of transmitter release shows that 4-AP enhances m by increasing n and not p.

Cited by 23 publications

References 24 publications

Mechanisms of Neuromodulation as Dissected Using Sr2+ at Motor Nerve Endings

Mechanisms of Neuromodulation as Dissected Using Sr2+ at Motor Nerve Endings

Action of 4-aminopyridine on the cerebral circulation

Effects of 4-Aminopyridine on Saxitoxin Intoxication

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Product

Resources

About

Mechanisms of Neuromodulation as Dissected Using Sr²⁺ at Motor Nerve Endings

Mechanisms of Neuromodulation as Dissected Using Sr²⁺ at Motor Nerve Endings