title: Endogenous protein phosphatase 1 runs down gap junctional communication of rat ventricular myocytes.
abstract: Gap junctional channels are essential for normal cardiac impulse propagation. In ventricular myocytes of newborn rats, channel opening requires the presence of ATP to allow protein kinase activities; otherwise, channels are rapidly deactivated by the action of endogenous protein phosphatases (PPs). The lack of influence of Mg(2+) and of selective PP2B inhibition is not in favor of the involvements of Mg(2+)-dependent PP2C and PP2B, respectively, in the loss of channel activity. Okadaic acid (1 microM) and calyculin A (100 nM), both inhibitors of PP1 and PP2A activities, significantly retarded the loss of channel activity. However, a better preservation was obtained in the presence of selective PP1 inhibitors heparin (100 microg/ml) or protein phosphatase inhibitor 2 (I2; 100 nM). Conversely, the stimulation of endogenous PP1 activity by p-nitrophenyl phosphate, in the presence of ATP, led to a progressive fading of junctional currents unless I2 was simultaneously added. Together, these results suggest that a basal phosphorylation-dephosphorylation turnover regulates gap junctional communication which is rapidly deactivated by PP1 activity when the phosphorylation pathway is hindered.
authors.affiliation: Physiologie Cellulaire, Unité Mixte de Recherche Centre National de Recherche Scientifique 6558, Université de Poitiers, 86022 Poitiers, France.
authors.forename: F
authors.initials: F
authors.lastname: Duthe
authors.forename: I
authors.initials: I
authors.lastname: Plaisance
authors.forename: D
authors.initials: D
authors.lastname: Sarrouilhe
authors.forename: J C
authors.initials: JC
authors.lastname: Hervé
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D054645:Protein Phosphatase 1; D051381:Rats; D017208:Rats, Wistar; D016276:Ventricular Function
chemical_list: D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D002118:Calcium