Glutamate Release Through Glial Gap-Junction Hemichannels

Science's STKE  20 May 2003:
Vol. 2003, Issue 183, pp. tw193-TW193
DOI: 10.1126/stke.2003.183.tw193

Ye et al. investigated the role of gap-junction hemichannels in astrocytes and discovered that they mediated glutamate release; regulation of astrocyte hemichannel activity could thus modulate levels of extracellular glutamate in the central nervous system. Abnormal increases in extracellular glutamate, the principal excitatory neurotransmitter in brain, have been implicated in excitotoxic cell death. Under normal conditions, astrocytes accumulate glutamate, which helps to maintain low extracellular concentrations. Gap junctions, formed by aligned hemichannels on adjacent cells, can mediate the passage of molecules between some cell types, including glia. Unopposed hemichannels have been identified in astrocytes; their functions, however, have been unclear. Ye at al. used immunocytochemistry to detect hemichannels in cultured rat hippocampal astrocytes and confirmed their functionality by measuring increased uptake of a fluorescent dye after exposure to nominally divalent cation-free saline (DFCS). Dye permeability was sensitive to gap-junction blockers. The authors monitored changes in extracellular and intracellular glutamate concentration, under different ionic conditions and in the presence or absence of various pharmacological agents, and determined that glutamate efflux in response to DFCS occurred through hemichannels. Increased glutamate efflux was accompanied by a decrease in glutamate uptake, likely secondary to a disruption of ionic gradients associated with hemichannel opening. Removal of divalent cations also elicited gap-junction-blocker-sensitive release of glutamate and other amino acids from mouse optic nerve (a white matter preparation). These data suggest that astrocytes could release glutamate through hemichannels in response to low extracellular divalent cation concentration in vivo and thereby contribute to various neuropathologies.

Z.-C. Ye, M. S. Wyeth, S. Baltan-Tekkok, B. R. Ransom, Functional hemichannels in astrocytes: A novel mechanism of glutamate release. J. Neurosci. 23, 3588-3596 (2003). [Abstract] [Full Text]