Novel role for prepatterned nicotinic acetylcholine receptors during myogenesis.
BACKGROUND
Before the nerve contacts the skeletal muscle, the nicotinic acetylcholine receptors (nAChRs) form aggregates known as prepatterned clusters. We investigated their role in the occurrence of Ca(2+) spikes and twitching during myogenesis.


METHODS
Cultured mouse myotubes were used as cell models. Cells were subjected to a combination of immunostaining, Ca(2+) imaging and electrophysiological analysis.


RESULTS
A single prepatterned nAChR cluster per myotube was generally detected. A correlation between formation of the prepatterned clusters and occurrence of Ca(2+) spikes and twitching was observed. Increase in size of the prepatterned clusters raised the frequency of Ca(2+) spikes and twitching. Blockade of the electrical activity triggered by the autocrine activation of prepatterned nAChR induced over-numbered nAChR clusters.


CONCLUSIONS
Prepatterned nAChR aggregation is required for Ca(2+) spikes and twitching of developing myotubes. Moreover, prepatterned nAChR-driven electrical activity preserves the distribution of nAChRs, mimicking the effect of synaptic activity before innervation.
Department of Life Sciences and Centre for Neuroscience BRAIN, University of Trieste, Trieste, Italy.
Annalisa
A
Bernareggi
Elisa
E
Luin
Elena
E
Formaggio
Guido
G
Fumagalli
Paola
P
Lorenzon
D000818:Animals; D001549:Benzamides; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000068877:Imatinib Mesylate; D051379:Mice; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011978:Receptors, Nicotinic; D000068877:Imatinib Mesylate; D002118:Calcium