Na,K-ATPase generates calcium oscillations in hippocampal astrocytes

Na,K-ATPase maintains not only ionic homeostasis, but also participates in a multiprotein complex mediating intracellular signalling. We show that ouabain, a specific ligand for Na,K-ATPase, evokes calcium oscillations in hippocampal astrocytes in primary cultures. Coimmunoprecipitation studies suggest that the mechanism underlying these calcium oscillations involves a multiprotein complex consisting of ankyrin-B, the inositol 1,4,5-trisphosphate receptor and Na,K-ATPase. The ouabain/Na,K-ATPase multi-protein complex induced calcium-dependent downstream activation of the transcription factor nuclear factor-kappaB. Calcium oscillations and nuclear factor-kappaB activation were blocked following intracellular calcium store depletion. Thus, the specific Na,K-ATPase ligand ouabain induced inositol 1,4,5-trisphosphate receptor-dependent calcium oscillations in hippocampal astrocytes, which mediates nuclear factor-kappaB activation.