Protein kinase A-Iα regulates Na,K-ATPase endocytosis in alveolar epithelial cells exposed to high CO2 concentrations

Emilia Lecuona*, Haiying Sun, Jiwang Chen, Humberto E. Trejo, Margaret A. Baker, Jacob I. Sznajder

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Elevated concentrations of CO2 (hypercapnia) lead to alveolar epithelial dysfunction by promoting Na,K-ATPase endocytosis. In the present report, we investigated whether the CO2/HCO3- activated soluble adenylyl cyclase (sAC) regulates this process. We found that hypercapnia increased the production of cyclic adenosine monophosphate (cAMP) and stimulated protein kinase A (PKA) activity via sAC, which was necessary for Na,K-ATPase endocytosis. During hypercapnia, cAMP was mainly produced in specific microdomains in the proximity of the plasma membrane, leading to PKA Type Ia activation. In alveolar epithelial cells exposed to high CO2 concentrations, PKA Type Iα regulated the time-dependent phosphorylation of the actin cytoskeleton component α-adducin at serine 726. Cells expressing small hairpin RNA for PKAc, dominant-negative PKA Type Iα, small interfering RNA for α-adducin, and α-adducin with serine 726 mutated to alanine prevented Na,K-ATPase endocytosis. In conclusion, we provide evidence for a new mechanism by which hypercapnia via sAC, cAMP, PKA Type Iα, and α-adducin regulates Na, K-ATPase endocytosis in alveolar epithelial cells.

Original languageEnglish (US)
Pages (from-to)626-634
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Issue number5
StatePublished - May 2013


  • Hypercapnia
  • Na,K-ATPase
  • PKA Type Iα
  • Soluble adenylyl cyclase
  • α-adducin

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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