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.
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.
Nojima
H
H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kimura
I
I
Kimura
M
M
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
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