The Cys-loop class of LGICs forms a superfamily of ionotropic receptors that includes two types of anion-permeable channels, which are represented by receptors for the neurotransmitters GABA (gamma-aminobutyric acid) and glycine, and allow negatively charged chloride ions to migrate through the cell membrane. Activation of these receptors in general leads to rapid inhibitory synaptic transmission. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in hyperpolarization of the neuron. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring. Mild inhibition of neuronal firing by drugs acting at the GABAA receptor causes a reduction of anxiety in the patient (an anxiolytic effect) while more pronounced inhibition induces general anesthesia. As a consequence of its high affinity binding to its natural inhibitor, strychnine, the GlyR was the first nicotinicoid receptor isolated from mammalian nervous tissue. Structurally and functionally, the glycine receptor is most closely related to the GABAA receptor. GlyRs are primarily expressed in spinal cord, brain stem, caudal brain, and retina. In adult neurons, the inhibitory chloride influx upon glycine receptor activation stabilizes the resting potential of the cell, rendering them electrically quiescent. Reduced channel expression and/or reduced activity of mutants often result in channelopathies involving muscle tone regulation, such as human startle disease (hyperekplexia).