Structures, Diversity and Pharmacology of Glycine Receptors and Transporters

Abstract

The amino acid glycine is highly concentrated in the ventral and dorsal horns of the spinal cord, in many brain stem nuclei, and in sensory relay stations such as the cochlear nucleus and the retina. Traditional physiological studies have shown that glycine is a major inhibitory neurotransmitter that performs a vital role in the control of both motor and sensory pathways (Aprison 1990). In presynaptic nerve terminals of glycinergic interneurons in spinal cord and brain stem, cytosolic glycine is concentrated in small clear synaptic vesicles by an H+-dependent vesicular glycine transporter. Excitation of these interneurons leads to the calcium-triggered fusion of these synaptic vesicles with the presynaptic plasma membrane, thus liberating glycine into the synaptic cleft. Glycine then binds to postsynaptic glycine receptors (GlyRs), causing gating of an integral anion channel that increases the chloride ion conductance of the plasma membrane. This postsynaptic action of glycine is selectively antagonized by the plant alkaloid strychnine. In mature neurons, where the chloride equilibrium potential approximates the resting potential, GlyR activation results in chloride ion influx. This neutralizes depolarization by sodium ion influx, thereby inhibiting the propagation of action potentials. However, a different response is found in the developing nervous system, where immature neurons contain very high intracellular chloride concentrations (Wang et al. 1994). Here, glycine-induced increases in chloride conductance cause CI-efflux, resulting in depolarization of the postsynaptic cell (see Reichling et al. 1994; Boehm et al. 1997).KeywordsGABAA ReceptorGlycine ReceptorGlycine TransporterNipecotic AcidInhibitory Glycine ReceptorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.