Hypotonic activation of volume-sensitive outwardly rectifying chloride channels in cultured PASMCs is modulated by SGK
| Autor: | Ilia A. Yamboliev, Burton Horowitz, Cian M. McCrudden, Joseph R. Hume, Yan-Ping Dai, Ge-Xin Wang |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Physiology Myocytes Smooth Muscle Protein Kinase C-epsilon Protein Serine-Threonine Kinases Pulmonary Artery Biology Muscle Smooth Vascular Immediate early protein Immediate-Early Proteins Phosphatidylinositol 3-Kinases Dogs Chloride Channels Proto-Oncogene Proteins Physiology (medical) Internal medicine medicine Animals Phosphorylation Threonine Protein kinase A Cells Cultured Protein Kinase C Protein kinase C Kinase Electric Conductivity Nuclear Proteins Cell biology Electrophysiology Endocrinology Hypotonic Solutions Chloride channel Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 287:H533-H544 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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