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J Neurophysiol (April 2, 2003). doi:10.1152/jn.01174.2002
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Submitted on December 30, 2002
Accepted on March 31, 2003

GABA-mediated trophic effect on oligodendrocytes requires Na-K-2Cl cotransport activity

Hao Wang1, Yiping Yan1, Douglas B. Kintner1, Christian Lytle2, and Dandan Sun3*

1 Neurosurgery, University of Wisconsin Medical School, Madison, WI, USA
2 Division of Biomedical Science, University of California-Riverside, Riverside, CA, USA
3 Neurosurgery, University of Wisconsin Medical School, Madison, WI, USA; Physiology, University of Wisconsin Medical School, Madison, WI, USA

* To whom correspondence should be addressed. E-mail: sun{at}neurosurg.wisc.edu.

The Na-K-2Cl cotransporter isoform1 (NKCC1) is present in many animal cells where it plays prominent roles in regulating cell volume and maintaining intracellular Cl- concentration ([Cl-]i) above electrochemical equilibrium. We show here that NKCC1 is present and active in cultured oligodendrocytes. Expression of NKCC1 in the rat spinal cord increased during development from postnatal day 6 through 21 in parallel with that of myelin basic protein. In cultured oligodendrocytes, 39% of the total K+(86Rb+) influx represented NKCC1 activity. Activation of GABAA receptors with muscimol produced a reduction in intracellular Cl- content, cell shrinkage, and a stimulation of NKCC1 activity. Muscimol also triggered an increase in intracellular Ca2+; this increase depended on NKCC1 activity. Survival of oligodendrocytes following withdrawal of growth factors was enhanced by muscimol; this effect also required NKCC1 activity. Our results suggest that NKCC1 functions in oligodendrocytes to maintain [Cl-]i above electrochemical equilibrium, and that NKCC1 is required for GABAergic trophic effects.




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