FIGURE 2.

Cell-type specific, neuronal and astroglial, stimuli, and mechanisms of D-serine release. Following depolarization, neurons release D-serine from the cytosol through the transporter asc-1. Note that neuronal depolarization is shown by the action potential discharges (utmost left). Astrocytes express a plethora of functional receptors, the activation of which is coupled to the release of D-serine. In many cases this would include a downstream activation of phospholipase C (PLC). Astrocytes release D-serine through Ca²⁺- and SNARE-dependent exocytosis along with that ocurring through alternative non-exocytotic pathways including volume-regulated anion channels (VRAC), ASCT, and likely through connexin 43 hemichannels (Cx43). The release of glial D-serine by exocytosis requires its uptake into glial secretory vesicles. The vesicular D-serine transporter is proposed to be a D-serine/chloride co-transporter. A spatial association of SR activity and D-serine vesicular transport results in a local and functional efficient coupling between D-serine synthesis and uptake. See text for details.