L. Cai and T. Du contributed equally to this article.
Astrocyte ERK phosphorylation precedes K+-induced swelling but follows hypotonicity-induced swelling
Version of Record online: 1 DEC 2010
© 2010 Japanese Society of Neuropathology
Volume 31, Issue 3, pages 250–264, June 2011
How to Cite
Cai, L., Du, T., Song, D., Li, B., Hertz, L. and Peng, L. (2011), Astrocyte ERK phosphorylation precedes K+-induced swelling but follows hypotonicity-induced swelling. Neuropathology, 31: 250–264. doi: 10.1111/j.1440-1789.2010.01172.x
- Issue online: 26 MAY 2011
- Version of Record online: 1 DEC 2010
- Received 6 November 2010; revised 11 September 2010 and accepted 20 September 2010; published online 1 December 2010.
- elevated potassium concentration;
- Na+,K+,2Cl- cotransporter;
Hypotonicity following water intoxication and/or salt loss leads to mainly astrocytic brain swelling. Astrocytic swelling also occurs following brain trauma or ischemia, together with an increase in extracellular K+ ([K+]o), stimulating a bumetanide/furosemide/ethacrynic acid-inhibitable cotransporter, NKCC1, that accumulates Na+ and K+ together with 2 Cl- and osmotically obliged water. Either type of swelling may become fatal and is associated with phosphorylation of extracellular regulated kinases 1 and 2 (ERK1/2). Only the swelling associated with elevated [K+]o, leads to an increase in astrocytic proliferation and in expression of the astrocytic marker, glial fibrillary acidic protein. These differences prompted us to investigate key aspects of the molecular pathways between hypotonicity-induced and high-K+-mediated swelling in primary cultures of mouse astrocytes. In the latter Ca2+-mediated, AG1478-inhibitable transactivation of the epidermal growth factor (EGF) receptor leads, via bumetanide-inhibitable activation of the mitogen activated protein (MAP) kinase pathway to ERK phosphorylation and to NKCC1-mediated swelling. In the former, inhibition of the MAP kinase pathway, but not of EGF receptor activation, abolishes ERK phosphorylation, but has no effect on swelling, indicating that activation of ERK is a result, not a cause, of the swelling.