title: The evidence of accelerative interaction between cAMP-dependent protein kinase and external calcium for the desensitization of nicotinic acetylcholine receptor channel in mouse skeletal muscle cells.
abstract: We investigated the effect of an activator (AA373) and an inhibitor (H-89) of cAMP-dependent protein kinase (PK-A) on the time-dependent decline in the opening frequency of acetylcholine (ACh)-activated channel currents using the cell-attached patch-clamp technique in adult mouse skeletal muscle cells. Although the time-dependent decline was independent of the presence of external Ca2+, it was accelerated by AA373 (1 mM) in 2.5 mM Ca2+ but not in Ca-free solution. The acceleration induced by AA373 was prevented by pretreatment with H-89 (3 microM). The accelerative effect of AA373 was also prevented by pretreatment with staurosporine (10 nM), a protein kinase C inhibitor, but not affected by pretreatment with KN-62 (5 microM), a calmodulin kinase II inhibitor. These results demonstrate that the desensitization of nicotinic ACh receptor channels was accelerated by PK-A in the presence of extracellular Ca2+. The accelerative effect of PK-A may be induced indirectly via the phosphorylation process that is influenced through the intracellular Ca2+ mobilization.
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nojima
authors.forename: I
authors.initials: I
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Kimura
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004553:Electric Conductivity; D062385:Hydroxybenzoates / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism* / Q000502:physiology; D019311:Staurosporine; D013449:Sulfonamides; D013997:Time Factors
chemical_list: D000470:Alkaloids; D062385:Hydroxybenzoates; D007546:Isoquinolines; D010879:Piperazines; D011978:Receptors, Nicotinic; D013449:Sulfonamides; C014261:3-(2'-hydroxy-4',5'-diethoxybenzoyl)propionic acid; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017868:Cyclic AMP-Dependent Protein Kinases; D019311:Staurosporine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium