Figure 1. Inhibitory and excitatory actions of glycine depend on the direction of glycine receptor (GlyR)-mediated  Cl^– flux. (a) In adult neurons, opening of GlyR channels causes  Cl^– influx into the cytoplasm of the depolarized cell, due to a low concentration of intracellular  Cl^–. This results in charge neutralization of intracellular Na⁺ ions, and thus inhibition of neuronal firing. (b) Owing to the high activity of a specific chloride exchange system, embryonic neurons contain a high concentration of intracellular  Cl^–. Opening of the GlyR channel therefore leads to  Cl^– efflux, and thereby an increase of intracellular positive charge, i.e. neuronal excitation.

Figure 2. Chemical structures of natural inhibitory amino acids and strychnine. Left, the glycine receptor agonists glycine, ã-alanine and taurine as well as -aminobutyric acid (GABA) are shown. Note different distances between positively and negatively charged head groups. Right, structure of strychnine. The aromatic ring positions indicated by arrows can be substituted without losing toxicity; this has been exploited for affinity purification and the synthesis of fluorescent derivatives.