Accumulation of Nav1 mRNAs at differentiating postsynaptic sites in rat soleus muscles

Acetylcholine receptors (AChRs) and voltage-gated sodium channels (Na(V)1s) accumulate at different times in the development of the murine neuromuscular junction (NMJ). We used in situ hybridization to study the relationship of Na(V)1 mRNA accumulation to this difference. mRNAs encoding both muscle Na(V)1 isoforms, Na(v)1.4 and Na(v)1.5, were first concentrated at NMJs at birth, when the proteins start to accumulate. Within 4 weeks, Na(v)1.4 mRNA increased 5-fold at the NMJ while Na(v)1.5 mRNA became undetectable. Na(V)1 mRNA accumulation occurred even if the nerve was cut at birth. Like AChR mRNA, Na(V)1 mRNA accumulated at denervated synaptic sites on regenerating muscles and in response to ectopically expressed neural agrin. Clustering of Na(V)1 at the NMJ follows that of its mRNA while AChR clustering precedes its mRNA clustering by several days. This suggests that factors other than local mRNA upregulation determine the timing of clustering of these two important postsynaptic ion channels.