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.
External pore residue mediates slow inactivation in mu 1 rat skeletal muscle sodium channels.
Balser JR, Nuss HB, Chiamvimonvat N, Pérez-García MT, Marban E, Tomaselli GF.
???displayArticle.abstract???
1. Upon depolarization, voltage-gated sodium channels assume non-conducting inactivated states which may be characterized as "fast' or "slow' depending on the length of the repolarization period needed for recovery. Skeletal muscle Na+ channel alpha-subunits expressed in Xenopus laevis oocytes display anomalous gating behaviour, with substantial slow inactivation after brief depolarizations. We exploited this kinetic behaviour to examine the structural basis for slow inactivation. 2. While fast inactivation in Na+ channels is mediated by cytoplasmic occlusion of the pore by III-IV linker residues, the structural features of slow inactivation are unknown. Since external pore-lining residues modulate C-type inactivation in potassium channels, we performed serial cysteine mutagenesis in the permeation loop (P-loop) of the rat skeletal muscle Na+ channel (mu 1) to determine whether similarly placed residues are involved in Na+ channel slow inactivation. 3. Wild-type and mutant alpha-subunits were heterologously expressed in Xenopus oocytes, and Na+ currents were recorded using a two-electrode voltage clamp. Slow inactivation after brief depolarizations was eliminated by the W402C mutation in domain I. Cysteine substitution of the homologous tryptophan residues in domains II, III and IV did not alter slow inactivation. 4. Analogous to the W402C mutation, coexpression of the wild-type alpha-subunit with rat brain Na+ channel beta 1-subunit attenuated slow inactivation. However, the W402C mutation imposed a delay on recovery from fast inactivation, while beta 1-subunit coexpression did not. We propose that the W402C mutation and the beta 1-subunit modulate gating through distinct mechanisms. 5. Removal of fast inactivation in wild-type alpha-subunits with the III-IV linker mutation I1303Q; F1304Q; M1305Q markedly slowed the development of slow inactivation. We propose that slow inactivation in Na+ channels involves conformational changes in the external pore. Mutations that affect fast and slow inactivation appear to interact despite their remote positions in the channel.
Adelman,
The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo pealei.
1969, Pubmed
Adelman,
The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo pealei.
1969,
Pubmed Armstrong,
Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons.
1971,
Pubmed Armstrong,
Inactivation of the sodium channel. II. Gating current experiments.
1977,
Pubmed Backx,
Molecular localization of an ion-binding site within the pore of mammalian sodium channels.
1992,
Pubmed Bennett,
A molecular basis for gating mode transitions in human skeletal muscle Na+ channels.
1993,
Pubmed
,
Xenbase Bezanilla,
Distribution and kinetics of membrane dielectric polarization. 1. Long-term inactivation of gating currents.
1982,
Pubmed Böhle,
Multimodal action of single Na+ channels in myocardial mouse cells.
1995,
Pubmed Cannon,
Modification of the Na+ current conducted by the rat skeletal muscle alpha subunit by coexpression with a human brain beta subunit.
1993,
Pubmed Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed HODGKIN,
A quantitative description of membrane current and its application to conduction and excitation in nerve.
1952,
Pubmed Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase Isom,
Functional co-expression of the beta 1 and type IIA alpha subunits of sodium channels in a mammalian cell line.
1995,
Pubmed
,
Xenbase Isom,
Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel.
1992,
Pubmed
,
Xenbase Krieg,
Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs.
1984,
Pubmed
,
Xenbase Kunkel,
Rapid and efficient site-specific mutagenesis without phenotypic selection.
1985,
Pubmed Kuo,
Na+ channels must deactivate to recover from inactivation.
1994,
Pubmed McPhee,
A mutation in segment IVS6 disrupts fast inactivation of sodium channels.
1994,
Pubmed
,
Xenbase Moorman,
Fast and slow gating of sodium channels encoded by a single mRNA.
1990,
Pubmed
,
Xenbase Nuss,
Coupling between fast and slow inactivation revealed by analysis of a point mutation (F1304Q) in mu 1 rat skeletal muscle sodium channels.
1996,
Pubmed
,
Xenbase Patlak,
Two modes of gating during late Na+ channel currents in frog sartorius muscle.
1986,
Pubmed Pérez-García,
Structure of the sodium channel pore revealed by serial cysteine mutagenesis.
1996,
Pubmed
,
Xenbase Quandt,
Burst kinetics of sodium channels which lack fast inactivation in mouse neuroblastoma cells.
1987,
Pubmed Rudy,
Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance.
1978,
Pubmed Sanger,
DNA sequencing with chain-terminating inhibitors.
1977,
Pubmed Stühmer,
Structural parts involved in activation and inactivation of the sodium channel.
1989,
Pubmed
,
Xenbase Tomaselli,
Molecular basis of permeation in voltage-gated ion channels.
1993,
Pubmed Trimmer,
Primary structure and functional expression of a mammalian skeletal muscle sodium channel.
1989,
Pubmed
,
Xenbase Valenzuela,
Gating of cardiac Na+ channels in excised membrane patches after modification by alpha-chymotrypsin.
1994,
Pubmed Vassilev,
Inhibition of inactivation of single sodium channels by a site-directed antibody.
1989,
Pubmed West,
A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.
1992,
Pubmed
,
Xenbase Zagotta,
Voltage-dependent gating of Shaker A-type potassium channels in Drosophila muscle.
1990,
Pubmed Zhou,
Multiple gating modes and the effect of modulating factors on the microI sodium channel.
1991,
Pubmed
,
Xenbase
