The desensitization gate of inhibitory Cys-loop receptors

• DOI: 10.1038/ncomms7829
• Publication Date: 2015-04-20T11:27:50Z
• Authors: Marc Gielen; Philip Thomas; Trevor G. Smart
• Keywords: Picrotoxin; Cys-loop receptors; Neurotransmitter receptor

Abstract Cys-loop neurotransmitter-gated ion channels are vital for communication throughout the nervous system. Following activation, these receptors enter into a desensitized state in which channel shuts even though neurotransmitter molecules remain bound. To date, molecular determinants underlying this most fundamental property of have remained elusive. Here we present generic mechanism desensitization GABA A (GABA Rs) and glycine (GlyRs), both mediate fast inhibitory synaptic transmission. Desensitization is regulated by interactions between second third transmembrane segments, affect lumen near its intracellular end. The R GlyR pore blocker picrotoxin prevented desensitization, consistent with deep channel-binding site overlapping physical gate.