Information is primarily conveyed in the nervous system through communication between nerve cells, or neurons, through a process known as synaptic transmission. In synaptic transmission, neurotransmitters migrate from the axon of the presynaptic neuron to the dendrites of the postsynaptic neuron, where they bind to neurotransmitter-operated ion channels, commonly called ligand-gated ion channels. When these channels open in response to the binding of neurotransmitters, specific ions are able to enter and leave the postsynaptic neuron, causing changes in the cell’s membrane potential and thus excitability.
The cys-loop receptor family is a class of ligand-gated ion channels that is currently being extensively studied in the neurobiology research community because of its potential clinical significance. Members of the cys-loop receptor family include serotonin receptor type 3, GABA receptors, nicotinic receptors, glycine receptors and zinc-activated cation channels. All receptors in the family have a pentameric structure, and each of the five subunits is composed of four transmembrane α-helixes (M1-M4). In addition, the extracellular structure to which ligands bind contains a loop of thirteen amino acids flanked by two cysteine residues that form a disulfide bond, which is why the family is referred to as the cys-loop receptors.
The dysfunction of these channels plays a key role in the origin of several psychiatric and neurological disorders, such as schizophrenia, epilepsy, smoking addiction and Alzheimer’s disease. These receptors are also primary targets for many clinically useful compounds, such as barbiturates, benzodiazepines and general anesthetics. Therefore, resear...
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...ys-loop ion channels. The researchers studied the Caenorhabditis elegans glutamate-gated chloride channel, which shares a 34% amino acid sequence identity with the human α1 glycine receptor. They elucidated the structure using crystallization techniques and fluorescence-detection size-exclusion chromatography. In 2011 another group of researchers also used crystallization techniques, this time to study nicotinic acetylcholine receptors. Their research shed light on the structure of the ligand-binding domain and the mechanism of allosteric modulation. This kind of research on the cys-loop receptor family primarily has applications in pharmacology. As researchers have a better understanding of the mechanism underlying agonist binding, they can produce better or more efficient pharmaceuticals that modulate these receptors and thus have significant clinical potential.
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