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

Aidar R. Gosmanov, Jennifer A. Wong, Donald Thomason

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Skeletal muscle Na+-K+-2Cl- cotransporter (NKCC) activity provides a potential mechanism for regulated K+ uptake. β-Adrenergic receptor (β-AR) activation stimulates skeletal muscle NKCC activity in a MAPK pathway-dependent manner. We examined potential G protein-coupled pathways for β-AR-stimulated NKCC activity. Inhibition of Gs-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 Gi-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 Ser259. These results demonstrate a novel, muscle phenotype-dependent mechanism for β-AR-mediated NKCC activation that involves both Gs and Gi protein-coupled mechanisms.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number4 52-4
StatePublished - Oct 2002

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Pertussis Toxin
Isoproterenol
GTP-Binding Proteins
Adrenergic Agents
Muscle
Skeletal Muscle
Chemical activation
8-Bromo Cyclic Adenosine Monophosphate
Phosphorylation
Cholera Toxin
Colforsin
Adrenergic Receptors
Phenotype
Muscles
Proteins

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Duality of G protein-coupled mechanisms for β-adrenergic activation of NKCC activity in skeletal muscle. / Gosmanov, Aidar R.; Wong, Jennifer A.; Thomason, Donald.

In: American Journal of Physiology - Cell Physiology, Vol. 283, No. 4 52-4, 10.2002.

Research output: Contribution to journalArticle

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