Astrocytes release glutamate upon hyperexcitation in the normal brain, and in response to pathologic insults such as ischemia and trauma. In our experiments, both hypotonic and ischemic stimuli caused the release of glutamate from cultured mouse astrocytes, which occurred with little or no contribution of gap junction hemichannels, vesicle-mediated exocytosis, or reversed operation of the Na-dependent glutamate transporter. Cell swelling and chemical ischemia activated, in cell-attached membrane patches, anionic channels with large unitary conductance (approximately 400 pS) and inactivation kinetics at potentials more positive than +20 mV or more negative than -20 mV. These properties are different from those of volume-sensitive outwardly rectifying (VSOR) Cl- channels, which were also expressed in these cells and exhibited intermediate unitary conductance (approximately 80 pS) and inactivation kinetics at large positive potentials of more than +40 mV. Both maxi-anion channels and VSOR Cl- channels were permeable to glutamate with permeability ratios of glutamate to chloride of 0.21 +/- 0.07 and 0.15 +/- 0.01, respectively. However, the release of glutamate was significantly more sensitive to Gd3+, a blocker of maxi-anion channels, than to phloretin, a blocker of VSOR Cl- channels. We conclude that these two channels jointly represent a major conductive pathway for the release of glutamate from swollen and ischemia-challenged astrocytes, with the contribution of maxi-anion channels being predominant.

Regulatory decrease in thymocyte volume under conditions of osmotic stress was abolished by potassium and chlorine channel blockers. Osmotic stress-activated chlorine channels belong to 2 pharmacological types. The maxi-anion channel is sensitive to Gd(3+). The volume-sensitive outwardly rectifying chlorine channel is inhibited with glybenclamide and phloretin.

No abstract