Protein kinase C-mediated changes in synaptic efficacy at the neuromuscular junction in vitro: the role of postsynaptic acetylcholine receptors.
Activation of a mouse in vitro neuromuscular synapse produces a reduction in synaptic efficacy which is greater for nonactivated than for activated inputs to the myotubes. This has been shown to require thrombin and thrombin receptor activation and to involve a protein kinase C (PKC)-mediated step. We show in the present work that phorbol ester activation of PKC produces physiological loss of synapses in a time- and dose-related manner. We observe, using quantitative imaging methods, a parallel loss of acetylcholine receptors (AChR) from synaptically functional neurite-associated receptor aggregates in nerve-muscle cocultures. Biochemical measurements of total AChR show that PKC activation reduces both AChR stability (increases receptor loss) and receptor insertion into the surface membrane. Taken together, the data suggest that PKC activation decreases the stability of AChR aggregates in the muscle surface membrane. We conclude that PKC plays a crucial role in activity-dependent synapse reduction and does so, at least in part, by altering AChR stability.
Lanuza
M A
MA
Unitat díHistologia i Neurobiologia, Facultat Medicina i Ciencies de la Salut, Universitat Rovira i Virgili, Reus, Spain.
Li
M X
MX
Jia
M
M
Kim
S
S
Davenport
R
R
Dunlap
V
V
Nelson
P G
PG
D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D018482:Muscle, Skeletal / Q000166:cytology / Q000294:innervation; D009469:Neuromuscular Junction / Q000166:cytology / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013569:Synapses / Q000737:chemistry / Q000201:enzymology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D011950:Receptors, Cholinergic; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate