Insulin-independent, MAPK-dependent stimulation of NKCC activity in skeletal muscle.
Na(+)-K(+)-Cl(-) cotransporter (NKCC) activity in quiescent skeletal muscle is modest. However, ex vivo stimulation of muscle for as little as 18 contractions (1 min, 0.3 Hz) dramatically increased the activity of the cotransporter, measured as the bumetanide-sensitive (86)Rb influx, in both soleus and plantaris muscles. This activation of cotransporter activity remained relatively constant for up to 10-Hz stimulation for 1 min, falling off at higher frequencies (30-Hz stimulation for 1 min). Similarly, stimulation of skeletal muscle with adrenergic receptor agonists phenylephrine, isoproterenol, or epinephrine produced a dramatic stimulation of NKCC activity. It did not appear that stimulation of NKCC activity was a reflection of increased Na(+)-K(+)-ATPase activity because insulin treatment did not stimulate NKCC activity, despite insulin's well-known stimulation of Na(+)-K(+)-ATPase activity. Stimulation of NKCC activity could be blocked by pretreatment with inhibitors of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2) activity, indicating that activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) MAPKs may be required. These data indicate a regulated NKCC activity in skeletal muscle that may provide a significant pathway for potassium transport into skeletal muscle fibers.
Wong
J A
JA
Department of Physiology, College of Medicine, University of Tennessee Health Science Center, 894 Union Ave., Memphis, TN 38163, USA.
Gosmanov
A R
AR
Schneider
E G
EG
Thomason
D B
DB
D000322:Adrenergic Agonists / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active; D002034:Bumetanide / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters
D000322:Adrenergic Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002070:Butadienes; D002352:Carrier Proteins; D004232:Diuretics; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007328:Insulin; D009570:Nitriles; D012414:Rubidium Radioisotopes; D028021:Sodium-Potassium-Chloride Symporters; C113580:U 0126; D002034:Bumetanide; D010656:Phenylephrine; D011433:Propranolol; D020928:Mitogen-Activated Protein Kinases; D007545:Isoproterenol; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D011224:Prazosin; D004837:Epinephrine