Cholinergic Sites in Skeletal Muscle. I. Denervation Effects

Richard R. Almon, Stanley H. Appel

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39 Scopus citations


Cholinergic interactions in systems derived from rat skeletal mixed muscle are detailed. The isotherms of the binding of [125I]diiodo-α-bungarotoxin over the range of 1010-10-5M toxin have been separated into a “nonspecific” component exclusive to the toxin and a “specific” component that binds both the toxin and d-tubocurarine. The “specific” component appears to reflect two independent sets of binding sites. One of the sets has an affinity constant on the order of 109M-1. Following denervation, the number of sites in this high-affinity set begins to increase after 3 days, reaches a peak (28-fold higher than normal) on the 8th day, and begins to decline. Similar results are obtained when sensitivity of this set to an antibody derived from patients with myasthenia gravis is examined. This sensitivity is reflected by the inhibition of the α-bungarotoxin binding by the myasthenic IgG fraction. Following denervation, sensitivity first appears on day 3 and progresses coincidentally with the increase in new sites in the set. The characteristics of this set suggest that it represents the acetylcholine receptor and that the new sites appearing during the course of denervation are extrajunctional receptor sites. The interaction with the myasthenic IgG indicates an antigenic difference between junctional and extrajunctional receptors. The second set of specific binding sites has an affinity constant on the order of 105M-1. The number of sites in this set increases only fivefold as a result of denervation. The increase also begins between days 2 and 3. The definition of this low affinity set of sites is not presently clear.

Original languageEnglish (US)
Pages (from-to)3662-3667
Number of pages6
Issue number17
StatePublished - Aug 1 1976

ASJC Scopus subject areas

  • Biochemistry


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