School of Physiology and Pharmacology, The University of New South Wales, Sydney, 2052, Australia; +Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia
Imoto et al. (1988) have shown that, as might have been expected, the three negatively charged rings of the transmembrane M2 region of the nicotinic acetylcholine receptor channel are major determinants of cation permeation through that channel. The inhibitory glycine receptor, also a member of the nicotinic acetylcholine ligand-gated ion channel superfamily, has two rings of positively charged arginine residues at positions 271 and 252 in the M2 regions of its [[alpha]] subunits. It has been predicted that these charged residues would analogously be determinants of anion permeation through the glycine receptor channel. Mutations of the 271 arginine residue to either of the uncharged amino acids, leucine or glutamine (associated with the neurological disorder, familial startle disease; Shiang et al., 1993), have a radical effect on the sensitivity of glycine activation. In addition, mutations of the arginine 271 residue to either leucine or glutamine decreased the whole cell conductance in homomeric 1 glycine receptor channels to about 20% of their wild type values, after correction for average cell receptor numbers (Rajendra et al., 1995). This result and those of other 271 mutations are basically similar to what may be predicted from equivalent mutations at the nicotinic acetylcholine receptor channel. Single channel measurements have also demonstrated that the drop in conductance with either the leucine or glutamine mutations reflects a shift to the lower sub-conductance states (see also Langosch et al., 1994).
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