Acetylcholinesterase and nicotinic acetylcholine receptor expression diverge in muscular dysgenic mice lacking the L-type calcium channel

L-type Ca2+ channels play critical roles in achieving stabilization of acetylcholinesterase (AChE) mRNA during myogenesis in C2-C12 skeletal muscle cells. To ascertain the importance of this signaling pathway in AChE expression during skeletal muscle development in the animal, we examined AChE mRNA levels in skeletal muscle and heart from control (+/+) and muscular dysgenic (mdg/mdg) mice that lack the skeletal, but not the cardiac, muscle L-type Ca2+ channels. RNase protection analysis showed 40-60% reductions in content of AChE mRNA in leg muscle, but not heart, from newborn and day 18 embryonic dysgenic mice. AChE activity was also reduced uniquely in skeletal muscle. In contrast to AChE transcripts, mRNA levels of the alpha-subunit of the nicotinic acetylcholine receptors (nAChRs) were increased in dysgenic skeletal muscle. Similar alterations in activity and mRNA levels of AChE were also observed from skeletal muscle cell lines derived from mdg mice. Because run-on transcription revealed no corresponding decrease in transcription rate, the decrease in mRNA content is likely a consequence of the inability of the dysgenic muscle cells to stabilize AChE mRNA during differentiation. These findings indicate that L-type Ca2+ channels play an important role in regulation of AChE expression during skeletal muscle development in vivo. The differential influence of muscle dysgenesis on mRNA levels of AChE and nAChRs provides additional evidence for distinct mechanisms of regulation of these two proteins.