Activators of protein kinase C enhance acetylcholine receptor desensitization in sympathetic ganglion neurons.
Recent studies suggest that phosphorylation may regulate the rate of desensitization of nicotinic acetylcholine (AcCho) receptors (AcChoR) in vertebrate muscle and Torpedo. It is not known if phosphorylation is involved in regulation of the neuronal AcChoR, however. In this study we examine the possibility that protein kinase C might regulate nicotinic AcChoR function in neurons. Several activators of protein kinase C (1-oleoyl-2-acetylglycerol, phorbol 12,13-diacetate, and phorbol 12,13-dibutyrate) were tested for their ability to modulate AcChoR function in embryonic chicken sympathetic ganglion neurons. Neurons were voltage-clamped at the resting potential, and the response to AcCho was tested before and after treatment with activators of protein kinase C. We find that all of these agents enhance the rate of decay of AcCho-induced current without affecting peak current amplitude or cellular input resistance. The drugs were ineffective if applied concurrently with AcCho: significant effects could be detected after 60 sec of pretreatment. A phorbol that does not increase protein kinase C activity (4 beta-phorbol) was ineffective in enhancing the decay of AcCho-induced current. Thus, the effects of these agents on AcChoR function are likely to be mediated by their interaction with C kinase, rather than by direct interaction with the AcChoR channel. Our data suggest that kinase C may regulate agonist-induced desensitization of the neuronal AcChoR channel.
D000818:Animals; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D005989:Glycerides / Q000494:pharmacology*; D009132:Muscles / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D014101:Torpedo
D004075:Diglycerides; D005989:Glycerides; D010703:Phorbol Esters; D011978:Receptors, Nicotinic; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C