Study of long term anticholinesterase therapy. Effects on neuromuscular transmission and on motor end plate fine structure

Andrew G Engel, E. H. Lambert, T. Santa

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Prostigmine (neostigmine methylsulfate) was administered subcutaneously in dosages of 0.4 mg per kilogram twice daily to rats for 42 to 149 days. Motor endplate fine structure was quantitatively analyzed in red and white muscle fibers, and in vitro microelectrode studies of neuromuscular transmission were performed in diaphragms of treated control animals. In treated animals degeneration of postsynaptic folds was often observed in endplates situated on red muscle fibers but infrequently in endplates situated on white muscle fibers. The abnormal folds became atrophic and collapsed residues of preexisting folds accumulated within the widened synaptic celfts. The postsynaptic membrane profile concentration was decreased by 29% in red muscle fibers and by 10% in white muscle fibers. The mean nerve terminal area, mean synaptic vesicle count per unit nerve terminal area, and mean postsynaptic area were not significantly affected by prostigmine treatment. Extension of a Schwann cell process into the primary synaptic cleft was observed in one or more regions of 8 of 16 soleus, 24 of 38 diaphragm, and 2 of 23 gastrocnemius endplates. The mean miniature endplate potential (MEPP) amplitude in the diaphragm was decreased by 29% below the control level. The MEPP frequency, the quantum content of the endplate potential, and the resting membrane potential were not affected by prostigmine treatment. The findings suggest that long term anticholinesterase therapy might eventually have an adverse side effect on neuromuscular transmission and could contribute to refractoriness in treatment in some cases of myasthenia gravis.

Original languageEnglish (US)
Pages (from-to)1273-1281
Number of pages9
JournalNeurology
Volume23
Issue number12
StatePublished - 1973

Fingerprint

Motor Endplate
Neostigmine
Cholinesterase Inhibitors
Slow-Twitch Muscle Fibers
Fast-Twitch Muscle Fibers
Diaphragm
Synaptic Vesicles
Schwann Cells
Myasthenia Gravis
Microelectrodes
Therapeutics
Membrane Potentials
Membranes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Study of long term anticholinesterase therapy. Effects on neuromuscular transmission and on motor end plate fine structure. / Engel, Andrew G; Lambert, E. H.; Santa, T.

In: Neurology, Vol. 23, No. 12, 1973, p. 1273-1281.

Research output: Contribution to journalArticle

@article{66b57b8ecf844fb19138451d3ff88373,
title = "Study of long term anticholinesterase therapy. Effects on neuromuscular transmission and on motor end plate fine structure",
abstract = "Prostigmine (neostigmine methylsulfate) was administered subcutaneously in dosages of 0.4 mg per kilogram twice daily to rats for 42 to 149 days. Motor endplate fine structure was quantitatively analyzed in red and white muscle fibers, and in vitro microelectrode studies of neuromuscular transmission were performed in diaphragms of treated control animals. In treated animals degeneration of postsynaptic folds was often observed in endplates situated on red muscle fibers but infrequently in endplates situated on white muscle fibers. The abnormal folds became atrophic and collapsed residues of preexisting folds accumulated within the widened synaptic celfts. The postsynaptic membrane profile concentration was decreased by 29{\%} in red muscle fibers and by 10{\%} in white muscle fibers. The mean nerve terminal area, mean synaptic vesicle count per unit nerve terminal area, and mean postsynaptic area were not significantly affected by prostigmine treatment. Extension of a Schwann cell process into the primary synaptic cleft was observed in one or more regions of 8 of 16 soleus, 24 of 38 diaphragm, and 2 of 23 gastrocnemius endplates. The mean miniature endplate potential (MEPP) amplitude in the diaphragm was decreased by 29{\%} below the control level. The MEPP frequency, the quantum content of the endplate potential, and the resting membrane potential were not affected by prostigmine treatment. The findings suggest that long term anticholinesterase therapy might eventually have an adverse side effect on neuromuscular transmission and could contribute to refractoriness in treatment in some cases of myasthenia gravis.",
author = "Engel, {Andrew G} and Lambert, {E. H.} and T. Santa",
year = "1973",
language = "English (US)",
volume = "23",
pages = "1273--1281",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Study of long term anticholinesterase therapy. Effects on neuromuscular transmission and on motor end plate fine structure

AU - Engel, Andrew G

AU - Lambert, E. H.

AU - Santa, T.

PY - 1973

Y1 - 1973

N2 - Prostigmine (neostigmine methylsulfate) was administered subcutaneously in dosages of 0.4 mg per kilogram twice daily to rats for 42 to 149 days. Motor endplate fine structure was quantitatively analyzed in red and white muscle fibers, and in vitro microelectrode studies of neuromuscular transmission were performed in diaphragms of treated control animals. In treated animals degeneration of postsynaptic folds was often observed in endplates situated on red muscle fibers but infrequently in endplates situated on white muscle fibers. The abnormal folds became atrophic and collapsed residues of preexisting folds accumulated within the widened synaptic celfts. The postsynaptic membrane profile concentration was decreased by 29% in red muscle fibers and by 10% in white muscle fibers. The mean nerve terminal area, mean synaptic vesicle count per unit nerve terminal area, and mean postsynaptic area were not significantly affected by prostigmine treatment. Extension of a Schwann cell process into the primary synaptic cleft was observed in one or more regions of 8 of 16 soleus, 24 of 38 diaphragm, and 2 of 23 gastrocnemius endplates. The mean miniature endplate potential (MEPP) amplitude in the diaphragm was decreased by 29% below the control level. The MEPP frequency, the quantum content of the endplate potential, and the resting membrane potential were not affected by prostigmine treatment. The findings suggest that long term anticholinesterase therapy might eventually have an adverse side effect on neuromuscular transmission and could contribute to refractoriness in treatment in some cases of myasthenia gravis.

AB - Prostigmine (neostigmine methylsulfate) was administered subcutaneously in dosages of 0.4 mg per kilogram twice daily to rats for 42 to 149 days. Motor endplate fine structure was quantitatively analyzed in red and white muscle fibers, and in vitro microelectrode studies of neuromuscular transmission were performed in diaphragms of treated control animals. In treated animals degeneration of postsynaptic folds was often observed in endplates situated on red muscle fibers but infrequently in endplates situated on white muscle fibers. The abnormal folds became atrophic and collapsed residues of preexisting folds accumulated within the widened synaptic celfts. The postsynaptic membrane profile concentration was decreased by 29% in red muscle fibers and by 10% in white muscle fibers. The mean nerve terminal area, mean synaptic vesicle count per unit nerve terminal area, and mean postsynaptic area were not significantly affected by prostigmine treatment. Extension of a Schwann cell process into the primary synaptic cleft was observed in one or more regions of 8 of 16 soleus, 24 of 38 diaphragm, and 2 of 23 gastrocnemius endplates. The mean miniature endplate potential (MEPP) amplitude in the diaphragm was decreased by 29% below the control level. The MEPP frequency, the quantum content of the endplate potential, and the resting membrane potential were not affected by prostigmine treatment. The findings suggest that long term anticholinesterase therapy might eventually have an adverse side effect on neuromuscular transmission and could contribute to refractoriness in treatment in some cases of myasthenia gravis.

UR - http://www.scopus.com/inward/record.url?scp=0015708681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0015708681&partnerID=8YFLogxK

M3 - Article

VL - 23

SP - 1273

EP - 1281

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 12

ER -