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Section of Neurobiology and Behavior, Cornell University, Ithaca, New York
Innervation of the neuromuscular junction
(nmj) affects the stability of acetylcholine receptors
(AChRs). A neural factor that could affect AChR stabilization was studied using cultured muscle cells since
they express two distinct populations of AChRs similar
to those seen at the nmjs of denervated muscle. These two AChR populations are (in a ratio of 9 to 1) a rapidly degrading population (Rr) with a degradation half-life of ~1 d and a slowly degrading population (Rs) that
can alternate between an accelerated form (half-life
~3-5 d) and a stabilized form (half-life ~10 d), depending upon the state of innervation of the muscle.
Previous studies have shown that elevation of intracellular cAMP can stabilize the Rs, but not the Rr. We
report here that in cultured rat muscle cells, exogenous
ATP stabilized the degradation half-life of Rr and possibly also the Rs. Furthermore, pretreatment with ATP
caused more stable AChRs to be inserted into the muscle membrane. Thus, in the presence of ATP, the degradation rates of the Rr and Rs overlap. This suggests
that ATP released from the nerve may play an important role in the regulation of AChR degradation. Treatment with either the cAMP analogue dibutyryl-cAMP (dB-cAMP) or the calcium mobilizer ryanodine caused
the ATP-stabilized Rr to accelerate back to a half-life
of 1 d. Thus, at least three signaling systems (intracellular cAMP, Ca2+, and extracellular ATP) have the potential to interact with each other in the building of an
adult neuromuscular junction.
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