Facilitatory effects of 4-aminopyridine on neuromuscular transmission in disease states.
The in vitro effects of 4-aminopyridine (4-AP) on neuromuscular transmission were determined by microelectrode techniques in intercostal muscles from patients with myasthenia gravis (MG) and the Eaton-Lambert syndrome (ELS), and in forelimb muscles from rats with experimental autoimmune myasthenia gravis (EAMG). In MG and EAMG, the amplitudes of miniature endplate potentials (MEPPs) and endplate potentials (EPPs) were reduced, and there was increased sensitivity to the blocking action of d-tubocurarine (dTc). In ELS, MEPP amplitude was normal but the average number of acetylcholine quanta released by nerve impulses was reduced, causing subthreshold EPPs. In EAMG muscle, 4-AP produced dose-dependent increases in EPP amplitude and in the duration of indirectly elicited muscle action potentials but no changes in MEPP amplitude and resting membrane potential. 4-AP completely reversed the postsynaptic blockade produced by dTc and EAMG. 4-AP appears to facilitate neuromuscular transmission in EAMG, MG, and ELS by increasing the neurally evoked transmitter release, thus overcoming either the pre- or the postsynaptic neuromuscular blockade.
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Related Subject Headings
- Syndrome
- Synaptic Transmission
- Neuromuscular Junction
- Neuromuscular Diseases
- Neurology & Neurosurgery
- Myasthenia Gravis
- Motor Endplate
- Middle Aged
- Membrane Potentials
- Lung Neoplasms
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Syndrome
- Synaptic Transmission
- Neuromuscular Junction
- Neuromuscular Diseases
- Neurology & Neurosurgery
- Myasthenia Gravis
- Motor Endplate
- Middle Aged
- Membrane Potentials
- Lung Neoplasms