The Time Course of Transmitter at Glycinergic Synapses onto Motoneurons

The concentration of transmitter in the synaptic cleft and its clearance time are one of the main determinants of synaptic strength. We estimated the time course of glycine at rat lumbar motoneurons synapses in spinal cord slices by recording synaptic currents in the presence of a low-affinity competitive antagonist at glycine receptors [2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium (SR-95531)]. Data were analyzed by using the established activation mechanism for glycine receptors and our measurements of SR-95531 binding rates. We show that this technique alone is not sufficient to determine simultaneously the peak concentration of transmitter and its clearance time. However, we found that block of the glial glycine transporter prolongs the glycine transient. This observation puts additional constraints on the range of possible values of the time course of glycine, indicating that glycine reaches a peak concentration of 2.2-3.5 mM and is cleared from the cleft with a time constant of 0.6-0.9 ms.