STABILIZATION OF ACETYLCHOLINE-RECEPTORS BY EXOGENOUS ATP AND ITS REVERSAL BY CAMP AND CALCIUM

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 hal f-life of similar to 1 d and a slowly degrading population (Rs) that c an alternate between an accelerated form (half-life similar to 3-5 d) and a stabilized form (half-life similar to 10 d), depending upon the stale of innervation of the muscle. Previous studies have shown that e levation of intracellular cAMP can stabilize the Rs, but not the Rr. W e report here that in cultured rat muscle cells, exogenous ATP stabili zed the degradation half-life of Rr and possibly also the Rs. Furtherm ore, pretreatment with ATP caused more stable AChRs to be inserted int o the muscle membrane. Thus, in the presence of ATP, the degradation r ates of the Rr and Rs overlap, This suggests that ATP released from th e nerve may play an important role in the regulation of AChR degradati on. Treatment with either the cAMP analogue dibutyryl-cAMP (dB-cAMP) o r the calcium mobilizer ryanodine caused the ATP-stabilized Rr to acce lerate back to a half-life of 1 d. Thus, at least three signaling syst ems (intracellular cAMP, Ca2+, and extracellular ATP) have the potenti al to interact with each other in the building of an adult neuromuscul ar junction.