ACTIVATION OF NICOTINIC ACETYLCHOLINE-RECEPTORS INCREASES THE RATE OFFUSION OF CULTURED HUMAN MYOBLASTS

1. Fusion of myogenic cells is important for muscle growth and repair. The aim of this study was to examine the possible involvement of nico tinic acetylcholine receptors (nAChR) in the fusion process of myoblas ts derived from postnatal human satellite cells. 2. Acetylcholine-acti vated currents (ACh currents) were characterized in pure preparations of freshly isolated satellite cells, proliferating myoblasts, myoblast s triggered to fuse and myotubes, using whole-cell and single-channel voltage clamp recordings. Also, the effect of cholinergic agonists on myoblast fusion was tested. 3. No nAChR were observed in freshly isola ted satellite cells. nAChR were first observed in proliferating myobla sts, but ACh current densities increased markedly only just before fus ion. At that time most mononucleated myoblasts had ACh current densiti es similar to those of myotubes. ACh channels had similar properties a t all stages of myoblast maturation. 4. The fraction of myoblasts that did not fuse under fusion-promoting conditions had no ACh current and thus resembled freshly isolated satellite cells. 5. The rate of myobl ast fusion was increased by carbachol, an effect antagonized by alpha- bungarotoxin, curare and decamethonium, but not by atropine, indicatin g that nAChR were involved. Even though a prolonged exposure to carbac hol led to desensitization, a residual ACh current persisted after sev eral days of exposure to the nicotinic agonist. 6. Our observations su ggest that nAChR play a role in myoblast fusion and that part of this role is mediated by the flow of ions through open ACh channels.