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Volume 17, Number 23, Issue of December 1, 1997 pp. 8937-8944

Subunit-Containing Acetylcholine Receptors in Myotubes Belong to the Slowly Degrading Population

Received Aug. 26, 1997; accepted Sept. 12, 1997.

Carlo Sala¹, James O'Malley², Rufeng Xu², Guido Fumagalli³, and Miriam M. Salpeter²

¹ Consiglio Nazionale delle Ricerche, Center of Cellular and Molecular Pharmacology, Department of Medical Pharmacology, University of Milan, 20129 Milan, Italy, ² Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853, and ³ Institute of Pharmacology, School of Medicine, University of Verona, 37134 Verona, Italy

Two types of muscle acetylcholine receptors (AChRs) can be distinguished on the basis of their degradation rates and sensitivities to innervation, muscle activity, and agents elevating intracellular cAMP. The first type (Rs), is present in a stable form (degradation t_1/2 = ~10 d) at the adult innervated neuromuscular junctions (NMJs). Rs can also exist in a less stable form (called accelerated Rs; t_1/2 = ~3-5 d) at denervated NMJs and in aneurally cultured myotubes; agents that increase intracellular cAMP reversibly modulate Rs stability. The second type of AChR is a rapidly degrading receptor (Rr) expressed only in embryonic and noninnervated muscles. Rr can be stabilized by ATP and not by cAMP. This study tested the hypothesis that the degradation properties unique to the Rs are attributable to the presence of the  subunit.

Immunoprecipitation and Western blot analysis of AChRs extracted from rat muscle cells in tissue culture showed that AChRs recognized by antibodies against the  subunit degraded as a single population with a half-life similar to that of the slow component, Rs, in these cells. In addition, as for Rs receptors in denervated NMJs and cultured muscle cell, the degradation rate of these -containing AChRs was stabilized by dibutyryl-cAMP. The data indicate that the -containing AChRs behave like Rs. Thus, the presence of the  subunit is sufficient for selecting an AChR molecule to the Rs pool.

Key words: AChR degradation; AChR subunit; myotubes; neuromuscular junction; immunoprecipitation; monoclonal antibodies; -bungarotoxin; cAMP

This article has been cited by other articles:

				Z.-Z. Wang, A. Mathias, M. Gautam, and Z. W. Hall Metabolic Stabilization of Muscle Nicotinic Acetylcholine Receptor by Rapsyn J. Neurosci., March 15, 1999; 19(6): 1998 - 2007. [Abstract] [Full Text] [PDF]

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