title: Autocrine activation of nicotinic acetylcholine receptors contributes to Ca2+ spikes in mouse myotubes during myogenesis.
abstract: It is widely accepted that nicotinic acetylcholine receptor (nAChR) channel activity controls myoblast fusion into myotubes during myogenesis. In this study we explored the possible role of nAChR channels after cell fusion in a murine cell model. Using videoimaging techniques we showed that embryonic muscle nAChR channel openings contribute to the spontaneous transients of intracellular concentration of Ca2+ ([Ca2+]i) and to twitches characteristic of developing myotubes before innervation. Moreover, we observed a choline acetyltransferase immunoreactivity in the myotubes and we detected an acetylcholine-like compound in the extracellular solution. Therefore, we suggest that the autocrine activation of nAChR channels gives rise to [Ca2+]i spikes and contractions. Spontaneous openings of the nAChR channels may be an alternative, although less efficient, mechanism. We report also that blocking the nAChRs causes a significant reduction in cell survival, detectable as a decreased number of myotubes in culture. This led us to hypothesize a possible functional role for the autocrine activation of the nAChRs. By triggering mechanical activity, such activation could represent a strategy to ensure the trophism of myotubes in the absence of nerves.
authors.affiliation: Department of Physiology and Pathology, University of Trieste, Via A. Fleming 22, I-34127 Trieste, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bandi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bernareggi
authors.forename: Micaela
authors.initials: M
authors.lastname: Grandolfo
authors.forename: Chiara
authors.initials: C
authors.lastname: Mozzetta
authors.forename: Gabriella
authors.initials: G
authors.lastname: Augusti-Tocco
authors.forename: Fabio
authors.initials: F
authors.lastname: Ruzzier
authors.forename: Paola
authors.initials: P
authors.lastname: Lorenzon
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002038:Bungarotoxins; D007473:Ion Channels; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D002118:Calcium