Gap junctions mediate intercellular spread of sodium between hippocampal astrocytes in situ
Article first published online: 24 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 60, Issue 2, pages 239–252, February 2012
How to Cite
Langer, J., Stephan, J., Theis, M. and Rose, C. R. (2012), Gap junctions mediate intercellular spread of sodium between hippocampal astrocytes in situ. Glia, 60: 239–252. doi: 10.1002/glia.21259
- Issue published online: 5 DEC 2011
- Article first published online: 24 OCT 2011
- Manuscript Accepted: 29 SEP 2011
- Manuscript Received: 10 MAR 2011
- Deutsche Forschungsgemeinschaft. Grant Numbers: SPP 1172 Ro 2327/4-3, SFB/TR3 C9, N01, SPP 1172 TH 1350/1-1
- EU. Grant Number: FP7-202167 NeuroGLIA
- gap junction;
Activation of glutamatergic synapses results in long-lasting sodium transients in astrocytes mediated mainly by sodium-dependent glutamate uptake. Sodium elevations activate Na+/K+-ATPase and glucose uptake by astrocytes, representing key signals for coupling glial metabolism to neuronal activity. Here, we analyzed the spread of sodium signals between astrocytes in hippocampal slice preparations. Stimulation of a single astrocyte resulted in an immediate sodium elevation that spread to neighboring astrocytes within a distance of ∼ 100 μm. Amplitude, slope, and propagation speed of sodium elevations in downstream cells decayed monotonically with increasing distance, indicative of a diffusion process. In contrast to sodium, calcium increases elicited by electrical stimulation were restricted to the stimulated cell and a few neighboring astrocytes. Pharmacological inhibition of mGluR1/5 slightly dampened the spread of sodium, whereas inhibition of glutamate uptake or purinergic receptors had no effect. Spread of sodium to neighboring cells was disturbed on pharmacological inhibition of gap junctions, reduced in animals at P4 and virtually omitted in Cx30/Cx43 double-deficient mice. In contrast to results obtained earlier in cultured astrocytes, our data thus indicate that calcium signaling and metabotropic glutamate receptors are supportive of, but not prerequisites for, the spread of sodium between hippocampal astrocytes in situ, whereas expression of Cx30 and Cx43 is essential. Cx30/Cx43-mediated sodium diffusion between astrocytes could represent a signal indicating increased metabolic needs, independent of concomitant calcium signaling. Spread of sodium might also serve a homeostatic function by supporting the re-establishment of steep sodium gradients and by lowering the metabolic burden imposed on single cells. © 2011 Wiley Periodicals, Inc.