PHAR 562 Lecture Notes - Lecture 5: Pentamer, Disulfide, Chemical Synapse

• School: McGill University
• Department: Pharmacology and Therapeutics
• Course: PHAR 562
• Professor: Derek Bowie

Document Summary

Many distinct subunits with many possible combinations (i. e. are highly diverse: there are hundreds of thousands of possible combinations. Mature receptors assemble as pentamers: differ from iglurs, which assemble as tetramers with a re-entrant loop; different architecture implies different mechanisms of action. Gabars have a cys loop on the extracellular portion (rather than a re-entrant loop) Activation mechanisms differ: gabars don"t involve crunching down of lbd as ligands bind between subunits (i. e. at the interface: have a similar arrangement to nachrs (which also assemble as pentamers) Gabaars are benzodiazepine-sensitive or -insensitive, found throughout cns: 1/2/3/5-containing gabars: always bdz-sensitive, 4/6-containing gabars: always bdz-insensitive, -containing gabars: usually bdz-insensitive. Gabaa- (or gabac-rs) are found in retina, form homomers: not highly abundant in the brain. Phasic & tonic signalling: phasic signaling: similar mechanism to iglurs, tonic signalling: Upon release from presynaptic terminal, some gaba diffuse into extrasynaptic space. Extrasynaptic -containing gabars is constantly activated: these have higher affinity for gaba.