The glycine receptor is a member of the cys-loop family of ligand-gated ion channels that mediate fast synaptic transmission in the central and peripheral nervous system. There have been some significant recent advances in determining which components of the structure of these receptor-channels mediate their functions of neurotransmitter binding, channel gating and ion permeation. This talk with initially review the general structure and physiological function of the glycine receptor, before focusing on the molecular determinants of ion permeation. Using a combination of site-directed mutagenesis and patch-clamp electrophysiology, our laboratory has characterised the amino acid residues in the second transmembrane domain that primarily determine the conductance and ion-charge selectivity of the glycine receptor. More recent experiments have investigated the potential role of residues in a novel intracellular region known as the lateral portals, as well as addressing the question of how counter-ion cations may permeate through these predominantly anionic channels. Time permiting, this talk may also briefly describe results investigating the determinants of ion-charge selectivity in a member of the P-loop family of cation channels, the cyclic nucleotide-gated channel.

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