Postnatal Development of Synaptic Glycine Receptors in Normal and Hyperglycinemic Rats

Abstract

The postnatal development of glycine synaptic receptors was studied. Strychnine binding to the synaptic membrane fraction is very low at birth, increases thereafter and reaches adult values at the 15th day in the brain and at the 30th day in the spinal cord. Throughout postnatal development, there are more glycine receptors in the spinal cord than in the brain. The development of receptors in the spinal cord displays a pattern similar to that reported previously for the glycine reuptake system in spinal cord slices and the activity of spinal cord glycine synthase. In rats with experimental hyperglycinemia, strychnine binding to spinal cord glycine receptors increases much more rapidly, reaching a level 1.5 times the control value by day 10. When the hyperglycinemia was induced after the 10th postnatal day, no effect on the glycine receptors was observed. This increased number of receptors could be explained by an effect of glycine on the synaptic stabilization process. No changes in the KD for strychnine were observed either during postnatal development or in hyperglycinemic rats. The KD remained approximately 10 nM in the spinal cord and 50 nM in the brain. Results are discussed with respect to the ontogeny of glycinergic synapses and the pathogenesis of nonketotic hyperglycinemia.