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Journal of Neuroscience, Vol 13, 2118-2125, Copyright © 1993 by Society for Neuroscience
The number of Na+ channels in cultured chick muscle is increased by ARIA, an acetylcholine receptor-inducing activity
G Corfas and GD Fischbach
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
ARIA is a glycoprotein purified from chick brain on the basis of its ACh
receptor-inducing activity (ARIA). In this study we present evidence that
ARIA increases the number of voltage-gated sodium channels in chick muscle
as well as the number of ACh receptors (AChRs). Exposure of chick myotubes
to ARIA increased by twofold the number of 3H-saxitoxin binding, an effect
that is comparable to the increase of AChRs assayed by
125I-alpha-bungarotoxin (125I-alpha-BTX) binding. We also documented
effects of ARIA on myoblasts: the number of 125I-alpha-BTX binding sites in
the mononucleated muscle cells was increased by 1.5-fold, and the peak
TTX-sensitive inward currents increased by the same amount. No change was
detected in the voltage dependence of channel activation, 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 channels are concentrated at motor end
plates, our results provide circumstantial evidence that ARIA may regulate
several genes expressed at developing neuromuscular junctions. Moreover,
the finding that ARIA's effects extend to mononucleated myoblasts suggests
that this protein may be important during the earliest stages of muscle
formation and innervation.
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