Regulation of Na(+)-K(+)-2Cl- cotransporter activity in rat skeletal muscle and intestinal epithelial cells.

A. R. Gosmanov, Donald Thomason

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In mammalian cells, Na(+)-K(+)-2Cl- cotransporter activity participates in regulation of ion and volume homeostasis. This makes NKCC indispensable for normal cell growth and proliferation. We recently reported the existence of two mechanisms that can regulate NKCC activity in mature skeletal muscle. In isosmotic conditions, signaling through ERK MAPK pathway is necessary, while inhibition of the cAMP-dependent protein kinase A (PKA) pathway stimulates NKCC activity during hyperosmotic challenge. Both pathways are involved in regulating cell proliferation in wide variety of cells of epithelial and non-epithelial origin, so we tested which pathway regulated NKCC activity in cultured cells. In cultured rat skeletal muscle (L6) and intestinal epithelial (IEC-6) cells, NKCC activity in the basal state comprised 30 to 50% of total potassium influx, assessed as bumetanide-sensitive 38Rb-uptake. This NKCC activity could not be abolished by inhibitors of ERK MAPK (PD98059 and U0126), PKC (GF109203X), or PI 3-K (wortmannin, LY294002). In L6 myoblasts and in IEC-6 cells, elevation of cAMP levels with isoproterenol or forskolin led to a 60% inhibition on NKCC activity. In contrast, incubation of IEC-6 cells with the PKA-inhibitor H-89 resulted in 50% increase of NKCC activity compared with the basal level. In conclusion, it appears that in cultured cells the cAMP--PKA pathway regulates NKCC activity. This resembles hyperosmotic regulation of NKCC activity.

Original languageEnglish (US)
Pages (from-to)812-816
Number of pages5
JournalTsitologiia
Volume45
Issue number8
StatePublished - Jan 1 2003

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Cyclic AMP-Dependent Protein Kinases
Skeletal Muscle
Epithelial Cells
Cultured Cells
Cell Proliferation
Bumetanide
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
MAP Kinase Signaling System
Myoblasts
Colforsin
Protein Kinase Inhibitors
Isoproterenol
Potassium
Homeostasis
Ions
Growth

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology

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Regulation of Na(+)-K(+)-2Cl- cotransporter activity in rat skeletal muscle and intestinal epithelial cells. / Gosmanov, A. R.; Thomason, Donald.

In: Tsitologiia, Vol. 45, No. 8, 01.01.2003, p. 812-816.

Research output: Contribution to journalArticle

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