title: Insulin and isoproterenol differentially regulate mitogen-activated protein kinase-dependent Na(+)-K(+)-2Cl(-) cotransporter activity in skeletal muscle.
abstract: Recent studies have demonstrated that p44/42(MAPK) extracellular signal-regulated kinase (ERK)1 and -2-dependent Na(+)-K(+)-2Cl(-) co-transporter (NKCC) activity may contribute to total potassium uptake by skeletal muscle. To study the precise mechanisms regulating NKCC activity, rat soleus and plantaris muscles were stimulated ex vivo by insulin or isoproterenol (ISO). Both hormones stimulated total uptake of the potassium congener (86)Rb by 25--70%. However, only ISO stimulated the NKCC-mediated (86)Rb uptake. Insulin inhibited the ISO-stimulated NKCC activity, and this counteraction was sensitive to the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 in the predominantly slow-twitch soleus muscle. Pretreatment of the soleus muscle with the phosphatidylinositol (PI) 3-kinase inhibitors wortmannin and LY294002 or with SB203580 uncovered an insulin-stimulated NKCC activity and also increased the insulin-stimulated phosphorylation of ERK. In the predominantly fast-twitch plantaris muscle, insulin-stimulated NKCC activity became apparent only after inhibition of PI 3-kinase activity, accompanied by an increase in ERK phosphorylation. PI 3-kinase inhibitors also abolished insulin-stimulated p38 MAPK phosphorylation in the plantaris muscle and Akt phosphorylation in both muscles. These data demonstrated that insulin inhibits NKCC-mediated transport in skeletal muscle through PI 3-kinase-sensitive and SB203580-sensitive mechanisms. Furthermore, differential activation of signaling cascade elements after hormonal stimulation may contribute to fiber-type specificity in the control of potassium transport by skeletal muscle.
authors.affiliation: Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Aidar R
authors.initials: AR
authors.lastname: Gosmanov
authors.forename: Donald B
authors.initials: DB
authors.lastname: Thomason
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000730:Androstadienes; D002867:Chromones; D007093:Imidazoles; D007328:Insulin; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; D012414:Rubidium Radioisotopes; D028021:Sodium-Potassium-Chloride Symporters; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D007545:Isoproterenol; C093642:SB 203580; D011188:Potassium; D000077191:Wortmannin