THE NUMBER OF NA-RECEPTOR INDUCING ACTIVITY( CHANNELS IN CULTURED CHICK MUSCLE IS INCREASED BY ARIA, AN ACETYLCHOLINE)

ARIA is a glycoprotein purified from chick brain on the basis of its A Ch receptor-inducing activity (ARIA). In this study we present evidenc e that ARIA increases the number of voltage-gated sodium channels in c hick muscle as well as the number of ACh receptors (AChRs). Exposure o f chick myotubes to ARIA increased by twofold the number of H-3-saxito xin binding, an effect that is comparable to the increase of AChRs ass ayed by I-125-alpha-bungarotoxin (I-125-alpha-BTX) binding. We also do cumented effects of ARIA on myoblasts: the number of I-125-alpha-BTX b inding sites in the mononucleated muscle cells was increased by 1.5-fo ld, and the peak TTX-sensitive inward currents increased by the same a mount. No change was detected in the voltage dependence of channel act ivation, in mean channel current, or in mean channel open time. Thus, the Na+ channel is the first molecule, other than AChR subunits, whose expression has been shown to be induced by ARIA. Since sodium channel s are concentrated at motor end plates, our results provide circumstan tial evidence that ARIA may regulate several genes expressed at develo ping neuromuscular junctions. Moreover, the finding that ARIA's effect s extend to mononucleated myoblasts suggests that this protein may be important during the earliest stages of muscle formation and innervati on.