Novel role for prepatterned nicotinic acetylcholine receptors during myogenesis

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. Muscle Nerve 46: 112–121, 2012