Hypotonic activation of volume-sensitive outwardly rectifying chloride channels in cultured PASMCs is modulated by SGK.
Am J Physiol Heart Circ Physiol
; 287(2): H533-44, 2004 Aug.
Article
in En
| MEDLINE
| ID: mdl-15277197
ABSTRACT
The serum- and glucocorticoid-inducible kinase (SGK) is a serine/threonine protein kinase (PK) transcriptionally regulated by corticoids, serum, and cell volume. SGK regulates cell volume of various cells by effects on Na(+) and K(+) transport through membrane channels. We hypothesized a role for SGK in the activation of volume-sensitive osmolyte and anion channels (VSOACs) in cultured canine pulmonary artery smooth muscle cells (PASMCs). Intracellular dialysis through the patch electrode of recombinant active SGK, but not kinase-dead Delta60-SGK-K127M, heat-inactivated SGK, or active Akt1, partially activated VSOACs under isotonic conditions. Dialysis of active SGK before cell exposure to hypotonic medium significantly accelerated the activation kinetics and increased the maximal density of VSOAC current. Exposure of PASMCs to hypotonic medium (230 mosM) activated phosphatidylinositol 3-kinases (PI3Ks) and their downstream targets Akt/PKB and SGK but not PKC-epsilon. Inhibition of PI3Ks with wortmannin reduced the activation rate and maximal amplitude of VSOACs. Immunoprecipitated ClC-3 channels were phosphorylated by PKC-epsilon but not by SGK in vitro, suggesting that SGK may activate VSOACs indirectly. These data indicate that the PI3K-SGK cascade is activated on hypotonic swelling of PASMCs and, in turn, affects downstream signaling molecules linked to activation of VSOACs.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Artery
/
Nuclear Proteins
/
Protein Serine-Threonine Kinases
/
Chloride Channels
/
Myocytes, Smooth Muscle
/
Hypotonic Solutions
/
Muscle, Smooth, Vascular
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
Am J Physiol Heart Circ Physiol
Journal subject:
CARDIOLOGIA
/
FISIOLOGIA
Year:
2004
Document type:
Article
Affiliation country:
Estados Unidos