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Tris+/Na+ permeability ratios of nicotinic acetylcholine receptors are reduced by mutations near the intracellular end of the M2 region.
Cohen BN, Labarca C, Czyzyk L, Davidson N, Lester HA.
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Tris+/Na+ permeability ratios were measured from shifts in the biionic reversal potentials of the macroscopic ACh-induced currents for 3 wild-type (WT), 1 hybrid, 2 subunit-deficient, and 25 mutant nicotinic receptors expressed in Xenopus oocytes. At two positions near the putative intracellular end of M2, 2' (alpha Thr244, beta Gly255, gamma Thr253, delta Ser258) and -1', point mutations reduced the relative Tris+ permeability of the mouse receptor as much as threefold. Comparable mutations at several other positions had no effects on relative Tris+ permeability. Mutations in delta had a greater effect on relative Tris+ permeability than did comparable mutations in gamma; omission of the mouse delta subunit (delta 0 receptor) or replacement of mouse delta with Xenopus delta dramatically reduced relative Tris+ permeability. The WT mouse muscle receptor (alpha beta gamma delta) had a higher relative permeability to Tris+ than the wild-type Torpedo receptor. Analysis of the data show that (a) changes in the Tris+/Na+ permeability ratio produced by mutations correlate better with the hydrophobicity of the amino acid residues in M2 than with their volume; and (b) the mole-fraction dependence of the reversal potential in mixed Na+/Tris+ solutions is approximately consistent with the Goldman-Hodgkin-Katz voltage equation. The results suggest that the main ion selectivity filter for large monovalent cations in the ACh receptor channel is the region delimited by positions -1' and 2' near the intracellular end of the M2 helix.
Adams,
The permeability of endplate channels to monovalent and divalent metal cations.
1980, Pubmed
Adams,
The permeability of endplate channels to monovalent and divalent metal cations.
1980,
Pubmed Baldwin,
Regulation of acetylcholine receptor transcript expression during development in Xenopus laevis.
1988,
Pubmed
,
Xenbase Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983,
Pubmed
,
Xenbase Charnet,
An open-channel blocker interacts with adjacent turns of alpha-helices in the nicotinic acetylcholine receptor.
1990,
Pubmed Claudio,
Nucleotide and deduced amino acid sequences of Torpedo californica acetylcholine receptor gamma subunit.
1983,
Pubmed Dani,
Open channel structure and ion binding sites of the nicotinic acetylcholine receptor channel.
1989,
Pubmed Dascal,
The use of Xenopus oocytes for the study of ion channels.
1987,
Pubmed
,
Xenbase Dwyer,
The permeability of the endplate channel to organic cations in frog muscle.
1980,
Pubmed Eisenman,
An introduction to molecular architecture and permeability of ion channels.
1987,
Pubmed Fiekers,
Voltage clamp analysis of the effect of cationic substitution on the conductance of end-plate channels.
1982,
Pubmed Gardner,
Nucleotide sequence of the epsilon-subunit of the mouse muscle nicotinic acetylcholine receptor.
1990,
Pubmed Giraudat,
Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: serine-262 of the delta subunit is labeled by [3H]chlorpromazine.
1986,
Pubmed Giraudat,
The noncompetitive blocker [(3)H]chlorpromazine labels segment M2 but not segment M1 of the nicotinic acetylcholine receptor alpha-subunit.
1989,
Pubmed Giraudat,
Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3H]chlorpromazine labels homologous residues in the beta and delta chains.
1987,
Pubmed Good,
Hydrogen ion buffers for biological research.
1966,
Pubmed Guy,
Amino acid side-chain partition energies and distribution of residues in soluble proteins.
1985,
Pubmed Huang,
Selectivity of cations and nonelectrolytes for acetylcholine-activated channels in cultured muscle cells.
1978,
Pubmed Hucho,
The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices M II of the receptor subunits.
1986,
Pubmed Imoto,
Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance.
1988,
Pubmed
,
Xenbase Isenberg,
Nucleotide sequence of the mouse muscle nicotinic acetylcholine receptor alpha subunit.
1986,
Pubmed Kullberg,
Multiple conductance classes of mouse nicotinic acetylcholine receptors expressed in Xenopus oocytes.
1990,
Pubmed
,
Xenbase LaPolla,
Isolation and characterization of a cDNA clone for the complete protein coding region of the delta subunit of the mouse acetylcholine receptor.
1984,
Pubmed Leonard,
Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor.
1988,
Pubmed
,
Xenbase Lester,
The permeation pathway of neurotransmitter-gated ion channels.
1992,
Pubmed Levitt,
Interpretation of biological ion channel flux data--reaction-rate versus continuum theory.
1986,
Pubmed Lo,
Influence of the gamma subunit and expression system on acetylcholine receptor gating.
1990,
Pubmed
,
Xenbase Maeno,
Permeability of the endplate membrane activated by acetylcholine to some organic cations.
1977,
Pubmed Miledi,
A calcium-dependent transient outward current in Xenopus laevis oocytes.
1982,
Pubmed
,
Xenbase Mishina,
Expression of functional acetylcholine receptor from cloned cDNAs.
,
Pubmed
,
Xenbase Mishina,
Location of functional regions of acetylcholine receptor alpha-subunit by site-directed mutagenesis.
,
Pubmed
,
Xenbase Noda,
Primary structures of beta- and delta-subunit precursors of Torpedo californica acetylcholine receptor deduced from cDNA sequences.
1983,
Pubmed Noda,
Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence.
1982,
Pubmed Oberthür,
The reaction site of a non-competitive antagonist in the delta-subunit of the nicotinic acetylcholine receptor.
1986,
Pubmed Oiki,
M2 delta, a candidate for the structure lining the ionic channel of the nicotinic cholinergic receptor.
1988,
Pubmed Oiki,
Bundles of amphipathic transmembrane alpha-helices as a structural motif for ion-conducting channel proteins: studies on sodium channels and acetylcholine receptors.
1990,
Pubmed Okamoto,
Antibiotics cause changes in the desensitization of ACh receptors expressed in Xenopus oocytes.
1991,
Pubmed
,
Xenbase PAULING,
The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain.
1951,
Pubmed Revah,
The noncompetitive blocker [3H]chlorpromazine labels three amino acids of the acetylcholine receptor gamma subunit: implications for the alpha-helical organization of regions MII and for the structure of the ion channel.
1990,
Pubmed Ritchie,
Ionic properties of the acetylcholine receptor in cultured rat myotubes.
1975,
Pubmed Sakmann,
Role of acetylcholine receptor subunits in gating of the channel.
,
Pubmed
,
Xenbase Sanchez,
Slow permeation of organic cations in acetylcholine receptor channels.
1986,
Pubmed Stroud,
Nicotinic acetylcholine receptor superfamily of ligand-gated ion channels.
1990,
Pubmed Trautmann,
Further investigations on the effect of denervation and pH on the conductance change at the neuromuscular junction of the frog.
1976,
Pubmed Villarroel,
Location of a threonine residue in the alpha-subunit M2 transmembrane segment that determines the ion flow through the acetylcholine receptor channel.
1991,
Pubmed
,
Xenbase White,
Mouse-Torpedo hybrid acetylcholine receptors: functional homology does not equal sequence homology.
1985,
Pubmed
,
Xenbase White,
Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes.
1990,
Pubmed
,
Xenbase Yoshii,
Equilibrium properties of mouse-Torpedo acetylcholine receptor hybrids expressed in Xenopus oocytes.
1987,
Pubmed
,
Xenbase Yu,
Mouse muscle nicotinic acetylcholine receptor gamma subunit: cDNA sequence and gene expression.
1986,
Pubmed
