TY - JOUR
T1 - Neuronal release of D-serine
T2 - A physiological pathway controlling extracellular D-serine concentration
AU - Rosenberg, Dina
AU - Kartvelishvily, Elena
AU - Shleper, Maria
AU - Klinker, Chanda M.C.
AU - Bowser, Michael T.
AU - Wolosker, Herman
PY - 2010/8
Y1 - 2010/8
N2 - D-Serine is thought to be a glia-derived transmitter that activates N-methyl D-aspartate receptors (NMDARs) in the brain. Here, we investigate the pathways for D-serine release using primary cultures, brain slices, and in vivo microdialysis. In contrast with the notion that D-serine is exclusively released from astrocytes, we found that D-serine is released by neuronal depolarization both in vitro and in vivo. Veratridine (50 μM) or depolarization by 40 mM KCl elicits a significant release of endogenous D-serine from primary neuronal cultures. Controls with astrocyte cultures indicate that glial cells are insensitive to veratridine, but release D-serine mainly by the opening of volume-regulated anion channels. In cortical slices perfused with veratridine, endogenous D-serine release is 10-fold higher than glutamate receptor-evoked release. Release of D-serine from slices does not require internal or external Ca2+, suggesting a nonvesicular release mechanism. To confirm the neuronal origin of D-serine, we selectively loaded neurons in cortical slices with D-[3H]serine or applied D-alanine, which specifically releases D-serine from neurons. Depolarization with veratridine promotes D-serine release in vivo monitored by high temporal resolution microdialysis of the striatum. Our data indicate that the neuronal pool of D-serine plays a major role in D-serine dynamics, with implications for the regulation of NMDAR transmission.
AB - D-Serine is thought to be a glia-derived transmitter that activates N-methyl D-aspartate receptors (NMDARs) in the brain. Here, we investigate the pathways for D-serine release using primary cultures, brain slices, and in vivo microdialysis. In contrast with the notion that D-serine is exclusively released from astrocytes, we found that D-serine is released by neuronal depolarization both in vitro and in vivo. Veratridine (50 μM) or depolarization by 40 mM KCl elicits a significant release of endogenous D-serine from primary neuronal cultures. Controls with astrocyte cultures indicate that glial cells are insensitive to veratridine, but release D-serine mainly by the opening of volume-regulated anion channels. In cortical slices perfused with veratridine, endogenous D-serine release is 10-fold higher than glutamate receptor-evoked release. Release of D-serine from slices does not require internal or external Ca2+, suggesting a nonvesicular release mechanism. To confirm the neuronal origin of D-serine, we selectively loaded neurons in cortical slices with D-[3H]serine or applied D-alanine, which specifically releases D-serine from neurons. Depolarization with veratridine promotes D-serine release in vivo monitored by high temporal resolution microdialysis of the striatum. Our data indicate that the neuronal pool of D-serine plays a major role in D-serine dynamics, with implications for the regulation of NMDAR transmission.
KW - Microdialysis
KW - NMDA receptor
KW - Neurotransmission
KW - Serine racemase
UR - http://www.scopus.com/inward/record.url?scp=77955803583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955803583&partnerID=8YFLogxK
U2 - 10.1096/fj.09-147967
DO - 10.1096/fj.09-147967
M3 - Article
C2 - 20371631
AN - SCOPUS:77955803583
SN - 0892-6638
VL - 24
SP - 2951
EP - 2961
JO - FASEB Journal
JF - FASEB Journal
IS - 8
ER -