Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Conductance mutations of the nicotinic acetylcholine receptor do not act by a simple electrostatic mechanism.
Kienker P, Tomaselli G, Jurman M, Yellen G.
???displayArticle.abstract???
Fixed negative charges in many cation channels raise the single-channel conductance, apparently by an electrostatic mechanism: their effects are accentuated in solutions of low ionic strength and attenuated at high ionic strength. The charges of specific amino acids near the ends of the proposed pore-lining M2 segment of the nicotinic acetylcholine receptor, termed the extracellular and cytoplasmic rings, have recently been shown to influence the single-channel K+ conductance (Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda and S. Numa. 1988. Nature 335:645-648). We examined whether these charges might act by a direct electrostatic effect on the energy of ions in the pore, rather than indirectly by inducing a structural change. To this end, we measured the conductances of charge mutants over a range of K+ concentrations (ionic strengths). As expected, we found that negative charge mutations raise the conductance, and positive charge mutations lower it. The effects of cytoplasmic-ring mutations are accentuated at low ionic strength, but they are not completely attenuated at high ionic strength. The effects of extracellular-ring mutations are independent of ionic strength. These results are inconsistent with the simplest electrostatic model. We suggest a modified model that qualitatively accounts for the data.
Apell,
Formation of ion channels by a negatively charged analog of gramicidin A.
1977, Pubmed
Apell,
Formation of ion channels by a negatively charged analog of gramicidin A.
1977,
Pubmed Apell,
Effects of surface charge on the conductance of the gramicidin channel.
1979,
Pubmed Bell,
Effects of phospholipid surface charge on ion conduction in the K+ channel of sarcoplasmic reticulum.
1984,
Pubmed Boulter,
Isolation of a clone coding for the alpha-subunit of a mouse acetylcholine receptor.
1985,
Pubmed Buonanno,
A universal oligonucleotide probe for acetylcholine receptor genes. Selection and sequencing of cDNA clones for the mouse muscle beta subunit.
1986,
Pubmed Cecchi,
A three-barrier model for the hemocyanin channel.
1981,
Pubmed Charnet,
An open-channel blocker interacts with adjacent turns of alpha-helices in the nicotinic acetylcholine receptor.
1990,
Pubmed Coronado,
Insulation of the conduction pathway of muscle transverse tubule calcium channels from the surface charge of bilayer phospholipid.
1986,
Pubmed Dani,
Ion-channel entrances influence permeation. Net charge, size, shape, and binding considerations.
1986,
Pubmed Dani,
Monovalent and divalent cation permeation in acetylcholine receptor channels. Ion transport related to structure.
1987,
Pubmed Dani,
Open channel structure and ion binding sites of the nicotinic acetylcholine receptor channel.
1989,
Pubmed Green,
Surface charges and ion channel function.
1991,
Pubmed Imoto,
Location of a delta-subunit region determining ion transport through the acetylcholine receptor channel.
,
Pubmed
,
Xenbase Imoto,
Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance.
1988,
Pubmed
,
Xenbase Klapper,
Focusing of electric fields in the active site of Cu-Zn superoxide dismutase: effects of ionic strength and amino-acid modification.
1986,
Pubmed Konno,
Rings of anionic amino acids as structural determinants of ion selectivity in the acetylcholine receptor channel.
1991,
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 Läuger,
Ion transport through pores: a rate-theory analysis.
1973,
Pubmed MacKinnon,
Functional modification of a Ca2+-activated K+ channel by trimethyloxonium.
1989,
Pubmed MacKinnon,
Role of surface electrostatics in the operation of a high-conductance Ca2+-activated K+ channel.
1989,
Pubmed Matthew,
Electrostatic effects in proteins.
1985,
Pubmed McLaughlin,
Divalent ions and the surface potential of charged phospholipid membranes.
1971,
Pubmed McLaughlin,
The electrostatic properties of membranes.
1989,
Pubmed Menestrina,
Interaction of tetanus toxin with lipid vesicles. Effects of pH, surface charge, and transmembrane potential on the kinetics of channel formation.
1989,
Pubmed Moczydlowski,
Effect of phospholipid surface charge on the conductance and gating of a Ca2+-activated K+ channel in planar lipid bilayers.
1985,
Pubmed Pappone,
Modifications of single acetylcholine-activated channels in BC3H-1 cells. Effects of trimethyloxonium and pH.
1990,
Pubmed Roeske,
Synthesis and channel properties of [Tau 16]gramicidin A.
1989,
Pubmed Sanchez,
Slow permeation of organic cations in acetylcholine receptor channels.
1986,
Pubmed Sigworth,
Chemical modification reduces the conductance of sodium channels in nerve.
1980,
Pubmed Tomaselli,
Mutations affecting agonist sensitivity of the nicotinic acetylcholine receptor.
1991,
Pubmed
,
Xenbase Toyoshima,
Ion channel of acetylcholine receptor reconstructed from images of postsynaptic membranes.
1988,
Pubmed van der Goot,
A 'molten-globule' membrane-insertion intermediate of the pore-forming domain of colicin A.
1991,
Pubmed Villarroel,
Threonine in the selectivity filter of the acetylcholine receptor channel.
1992,
Pubmed
,
Xenbase Worley,
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium.
1986,
Pubmed Yu,
Mouse muscle nicotinic acetylcholine receptor gamma subunit: cDNA sequence and gene expression.
1986,
Pubmed Zauhar,
A new method for computing the macromolecular electric potential.
1985,
Pubmed
