Duality of G protein-coupled mechanisms for beta -adrenergic activation of NKCC activity in skeletal muscle

• Published in: American Journal of Physiology: Cell Physiology 2002-10, Vol.283 (4), p.C1025-C1032
• Main Authors: Gosmanov, Aidar R, Wong, Jennifer A, Thomason, Donald B
• Format: Article
• Language: English
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Adrenergic beta-Agonists - pharmacology; Animals; Cyclic AMP-Dependent Protein Kinases - drug effects; Cyclic AMP-Dependent Protein Kinases - metabolism; Enzyme Activation - drug effects; Enzyme Activation - physiology; Enzyme Activators - pharmacology; Female; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; GTP-Binding Protein alpha Subunits, Gs - metabolism; GTP-Binding Proteins - metabolism; In Vitro Techniques; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Pertussis Toxin; Phosphorylation - drug effects; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-raf - metabolism; Rats; Receptors, Adrenergic, beta - metabolism; Signal Transduction - physiology; Sodium-Potassium-Chloride Symporters - drug effects; Sodium-Potassium-Chloride Symporters - metabolism; Virulence Factors, Bordetella - pharmacology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00096.2002

Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163 Skeletal muscle Na + -K + -2Cl cotransporter (NKCC) activity provides a potential mechanism for regulated K + uptake. -Adrenergic receptor ( -AR) activation stimulates skeletal muscle NKCC activity in a MAPK pathway-dependent manner. We examined potential G protein-coupled pathways for -AR-stimulated NKCC activity. Inhibition of G s -coupled PKA blocked isoproterenol-stimulated NKCC activity in both the slow-twitch soleus muscle and the fast-twitch plantaris muscle. However, the PKA-activating agents cholera toxin, forskolin, and 8-bromo-cAMP (8-BrcAMP) were not sufficient to activate NKCC in the plantaris and partially stimulated NKCC activity in the soleus. Isoproterenol-stimulated NKCC activity in the soleus was abolished by pretreatment with pertussis toxin (PTX), indicating a G i -coupled mechanism. PTX did not affect the 8-BrcAMP-stimulated NKCC activity. PTX treatment also precluded the isoproterenol-mediated ERK1/2 MAPK phosphorylation in the soleus, consistent with NKCC's MAPK dependency. Inhibition of isoproterenol-stimulated ERK activity by PTX treatment was associated with an increase in Akt activation and phosphorylation of Raf-1 on the inhibitory residue Ser 259 . These results demonstrate a novel, muscle phenotype-dependent mechanism for -AR-mediated NKCC activation that involves both G s and G i protein-coupled mechanisms. potassium; mitogen-activated protein kinases; protein kinase A; pertussis toxin; Raf-1