Glycinergic nerve endings in hippocampus and spinal cord release glycine by different mechanisms in response to identical depolarizing stimuli.
Studies on hippocampal glycine release are extremely rare. We here investigated release from mouse hippocampus glycinergic terminals selectively pre-labelled with [(3)H]glycine through transporters of the GLYT2 type. Purified synaptosomes were incubated with [(3)H]glycine in the presence of the GLYT1 blocker NFPS to abolish uptake (approximately 30%) through GLYT1. The non-GLYT1-mediated uptake was entirely sensitive to the GLYT2 blocker Org25543. Depolarization during superfusion with high-K(+) (15-50 mmol/L) provoked overflows totally dependent on external Ca(2+), whereas in the spinal cord the 35 or 50 mmol/L KCl-evoked overflow (higher than that in hippocampus) was only partly dependent on extraterminal Ca(2+). In the hippocampus, the Ca(2+)-dependent 4-aminopyridine (1 mmol/L)-evoked overflow was five-fold lower than that in spinal cord. The component of the 10 mumol/L veratridine-induced overflow dependent on external Ca(2+) was higher in the hippocampus than that in spinal cord, although the total overflow in the hippocampus was only half of that in the spinal cord. Part of the veratridine-evoked hippocampal overflow occurred by GLYT2 reversal and part by bafilomycin A(1)-sensitive exocytosis dependent on cytosolic Ca(2+) generated through the mitochondrial Na(+)/Ca(2+) exchanger. As glycine sites on NMDA receptors are normally not saturated, understanding mechanisms of glycine release should facilitate pharmacological modulation of NMDA receptor function.
Luccini
Elisa
E
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Romei
Cristina
C
Raiteri
Luca
L
D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012521:Sarcosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
C435025:N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-3-(4'-phenylphenoxy)propyl)sarcosine; D011189:Potassium Chloride; D014701:Veratridine; D005998:Glycine; D012521:Sarcosine