Single channel evidence for a cytoskeletal defect involving acetylcholine receptors and calcium influx in cultured dystrophic (mdx) myotubes.
Single channel events that exhibited the conductance, event duration, and ion selectivity characteristics of calcium leakage activity (CLA) were recorded in association with acetylcholine receptor (AChR) activity in cultured nondystrophic myotubes. The CLA was observed in the presence or absence of acetylcholine (ACh), and at normal or elevated concentrations of calcium. In contrast to results from nondystrophic myotubes, cell-attached patches from several cultured dystrophic (mdx) myotubes exhibited 100% CLA with no AChR activity, even though ACh was present in the pipette solution. Acquisition of an inside-out patch from these membrane areas produced a profound decrease in CLA and the appearance of AChR events exhibiting typical conductance and event duration characteristics. These results suggest that CLA in dystrophic muscle is produced, in part, by unusual physical interactions between AChRs and the dystrophic cytoskeleton that are mediated by the action of intracellular modulators responsible for aggregating and stabilizing AChRs.
Carlson
C G
CG
Department of Physiology, Kirksville College of Osteopathic Medicine, Missouri 63501, USA.
Officer
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D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D046508:Culture Techniques; D003599:Cytoskeleton / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011950:Receptors, Cholinergic / Q000378:metabolism; D012016:Reference Values
D011950:Receptors, Cholinergic; D000109:Acetylcholine; D002118:Calcium