Cell Swelling Triggers Glutamate Release

Science's STKE  15 Nov 2005:
Vol. 2005, Issue 310, pp. tw403
DOI: 10.1126/stke.3102005tw403

Astrocytes are becoming recognized as active participants in modulating neuronal activity. Indeed, astrocytes accumulate glutamate and release this neurotransmitter in response to purinergic receptor activation by ATP. Takano et al. provide evidence that ATP triggers transient cell swelling, which activates volume-sensitive channels, allowing glutamate and other osmolytes, such as aspartate and taurine, to be released. Cell swelling was detected in three different assays. In the presence of hypertonic medium, ATP-stimulated release of glutamate was abolished. Release of glutamate, taurine, and aspartate also required increased calcium concentrations and was blocked by calcium chelators. Whole-cell currents were measured in cultured astrocytes and showed an ATP-stimulated inward current mediated by glutamate release (under conditions where glutamate was the only possible charge carrier). Finally, a similar ATP-stimulated and calcium-dependent glutamate current was recorded in astrocytes in hippocampal slices using two-photon microscopy and whole-cell current clamp. Thus, glutamate and other osmolyte amino acids appear to be released from astrocytes by a volume-sensitive channel that is activated in response to cell swelling caused by activation of purinergic receptors. The strongest evidence against calcium-dependent vesicular release is the inhibition of release in the presence of hypertonic medium, which typically stimulates vesicular release.

T. Takano, J. Kang, J. K. Jaiswal, S. M. Simon, J. H.-C. Lin, Y. Yu, Y. Li, J. Yang, G. Dienel, H. R. Zielke, M. Nedergaard, Receptor-mediated glutamate release from volume sensitive channels in astrocytes. Proc. Natl. Acad. Sci. U.S.A. 102, 16466-16471 (2005). [Abstract] [Full Text]