Figure 3.

Mechanisms of glutamate release from astrocytes. Glutamate (orange) can be released from astrocytes via the reverse action of GLT-1 (green) via the action of cystine glutamate exchange (blue circle with red and blue arrows), through a swelling-induced release via volume regulated anion channels (VRAC) (pink), through purine activated ion channels (P2X7) (red), through gap-junctions or hemichannels (yellow), and through Ca²⁺-dependent vesicular release (grey synaptic-like microvesicles [SLMV]). Potential sources for increased [Ca²⁺]i are also shown above as these increases in Ca²⁺ concentration could result in vesicular glutamate release. Activation of transient receptor potential canonical receptors (TRPC) (green) causes direct calcium influx, as does the activation of inotropic glutamate receptors (iGluR) (purple), P2X7 purine receptors, and voltage-gated calcium channels (VGCC) (yellow). G-protein coupled receptors like metabotropic glutamate receptors (mGLuR) (red) and metabotropic purine receptors (P2Y) (orange) activate phospholipase C (PLC) cleaving PIP2 into IP3 and DAG leading to the activation of IP3 receptors (IP3R2) (blue) located on the endoplasmic reticulum (gray). Once activated these receptors release Ca²⁺ into the cytosol from intracellular stores possibly enhancing [Ca²⁺]i to levels that would influence Ca²⁺-mediated vesicular release of glutamate from astrocytes.