localization of GlyRs and the pharmacological profile of glycinergic currents. Function Adults In mature adults, glycine is a inhibitory neurotransmitter found in the spinal cord and regions of the brain. As it binds to a glycine receptor, a conformational change is induced, and the channel created by the receptor opens. As the channel opens, chloride ions are able to flow into the cell which results in hyperpolarization. In addition to this hyperpolarization which decreases the likelihood of action potential propagation, glycine is also responsible for decreasing the transmission of both inhibitory and excitatory neurotransmitters as it binds to its receptor. This is called the "shunting" effect and can be explained by Ohm's Law. As the receptor is activated, the membrane conductance is increased and the membrane resistance is decreased. According to Ohm's Law, as resistance decreases, so does voltage. A decreased postsynaptic voltage results in a decreased transmission of neurotransmitters. Embryos In developing embryos, glycine has the opposite effect as it does in adults. It is an excitatory neurotransmitter. This is due to the fact that chloride has a more positive equilibrium potential in early stages of life due to the high expression of NKCC1. This moves one sodium, one potassium and two chloride ions into the cell, resulting in a higher intracellular chloride concentration. When glycine binds to its receptor, the result is an efflux of chloride, instead of an influx as it happens in mature adults. The efflux of chloride causes the membrane potential to become more positive, or depolarized. As the cells mature, the K+-Cl- cotransporter 2 (KCC2) is expressed, which moves potassium and chloride out of the cell, decreasing the intracellular chloride concentration. This allows the receptor to switch to an inhibitory mechanism as described above for adults. Glycine receptors in diseases Disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions results in the rare neurological disorder, hyperekplexia. The disorder is characterized by an exaggerated response to unexpected stimuli which is followed by a temporary but complete muscular rigidity often resulting in an unprotected fall. Chronic injuries as a result of the falls are symptomatic of the disorder. A mutation in GLRA1 is responsible for some cases of stiff person syndrome. Ligands Agonists β-Alanine D-Alanine Gelsemine Glycine Hypotaurine Ivermectin L-Alanine L-Proline L-Serine Milacemide Quisqualamine Sarcosine Taurine THC L-Theanine Positive Allosteric Modulators Ethanol Toluene Antagonists Bicuculline Brucine Caffeine Levorphanol Picrotoxin Strychnine