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PMID: 1655812 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Effect of agrin on the distribution of acetylcholine receptors and sodium channels on adult skeletal muscle fibers in culture.

The Journal of cell biology ·Vol. 115 ·No. 3 ·1991-11-00 ·Pages 765-78

Lupa MT, Caldwell JH

Abstract

We used the loose patch voltage clamp technique and rhodamine-conjugated alpha-bungarotoxin to study the regulation of Na channel (NaCh) and acetylcholine receptor (AChR) distribution on dissociated adult skeletal muscle fibers in culture. The aggregate of AChRs and NaChs normally found in the postsynaptic membrane of these cells gradually fragmented and dispersed from the synaptic region after several days in culture. This dispersal was the result of the collagenase treatment used to dissociate the cells, suggesting that a factor associated with the extracellular matrix was responsible for maintaining the high concentration of AchRs and NaChs at the neuromuscular junction. We tested whether the basal lamina protein agrin, which has been shown to induce the aggregation of AChRs on embryonic myotubes, could similarly influence the distribution of NaChs. By following identified fibers, we found that agrin accelerated both the fragmentation of the endplate AChR cluster into smaller patches as well as the appearance of new AChR clusters away from the endplate. AChR patches which were fragments of the original endplate retained a high density of NaChs, but no new NaCh hotspots were found elsewhere on the fiber, including sites of newly formed AChR clusters. The results are consistent with the hypothesis that extracellular signals regulate the distribution of AChRs and NaChs on skeletal muscle fibers. While agrin probably serves this function for the AChR, it does not appear to play a role in the regulation of the NaCh distribution.

MeSH Terms
Agrin Animals Bungarotoxins/metabolism Kinetics Male Membrane Potentials/drug effects Motor Endplate/drug effects,physiology Muscles/drug effects,physiology Nerve Tissue Proteins/pharmacology Neuromuscular Junction/drug effects,physiology Organ Culture Techniques Rats Receptors, Cholinergic/drug effects,physiology Sodium Channels/drug effects,physiology Time Factors
Chemicals
Agrin Bungarotoxins Nerve Tissue Proteins Receptors, Cholinergic Sodium Channels
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lupa M T
University of Colorado Health Science Center, Department of Cellular and Structural Biology, Denver 80262.
Caldwell J H
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.115.3.765
Published
1991-11-00
Pages
765-78
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2289169
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.115.3.765 PMC Full Text View journal details
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