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

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+ (Rb-86(+)) influx represented NKCC1 activity. Activation of GABA A 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+, which depended on NKCC1 activity. Survival of oligodendrocytes following withdrawal of growth factors was enhanced by muscimol and 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.