Strychnine-sensitive glycine responses of neonatal rat hippocampal neurones

1. Intracellular recordings employing current and voltage clamp techniques were used to study the effects of glycine on rat CA3 hippocampal neurones during the first 3 weeks of postnatal (P) life. 2. Glycine (0.3-1 mM) depolarized neurones from rats less than 4 days old (P4). Neurones from older neonates (P5-P7) were hyperpolarized by glycine, whereas adult neurones were unaffected. 3. Both depolarizing and hyperpolarizing responses were associated with large conductance increases; they reversed polarity at a potential which changed with the extracellular chloride concentration. The responses persisted in tetrodotoxin (1 microM) or in a solution with a much reduced calcium concentration. 4. Strychnine (1 microM) but not bicuculline (10-50 microM) antagonized the effects of glycine. The action of strychnine was apparently competitive with a dissociation constant of 350 nM. 5. In voltage clamp experiments, glycine elicited a non-desensitizing outward current at -60 mV. When a maximal concentration of glycine was applied at the same time as gamma-aminobutyric acid (GABA), the conductance increase induced by the two agonists was additive, suggesting the activation of different populations of channels. 6. Concentrations of glycine lower than 100 microM did not affect membrane potential. However, at 30-50 microM glycine increased the frequency of spontaneous GABA-mediated synaptic responses; this action was not blocked by strychnine. 7. It is concluded that during the first 2 weeks of life glycine acts at strychnine-sensitive receptors to open chloride channels.