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.
???displayArticle.abstract???
The beta subunit (Kvbeta) of the Shaker family voltage-dependent potassium channels (Kv1) is a cytosolic protein that forms a permanent complex with the channel. Sequence and structural conservation indicates that Kvbeta resembles an aldo-keto reductase (AKR), an enzyme that catalyzes a redox reaction using an NADPH cofactor. A putative AKR in complex with a Kv channel has led to the hypothesis that intracellular redox potential may dynamically influence the excitability of a cell through Kvbeta. Since the AKR function of Kvbeta has never been demonstrated, a direct functional coupling between the two has not been established. We report here the identification of Kvbeta substrates and the demonstration that Kvbeta is a functional AKR. We have also found that channel function is modulated when the Kvbeta-bound NADPH is oxidized. Further studies of the enzymatic properties of Kvbeta seem to favor the role of Kvbeta as a redox sensor. These results suggest that Kvbeta may couple the excitability of the cell to its metabolic state and present a new avenue of research that may lead to understanding of the physiological functions of Kvbeta.
Accili,
Separable effects of human Kvbeta1.2 N- and C-termini on inactivation and expression of human Kv1.4.
1998, Pubmed,
Xenbase
Accili,
Separable effects of human Kvbeta1.2 N- and C-termini on inactivation and expression of human Kv1.4.
1998,
Pubmed
,
Xenbase
Accili,
Separable Kvbeta subunit domains alter expression and gating of potassium channels.
1997,
Pubmed
,
Xenbase
Askonas,
The kinetic mechanism catalysed by homogeneous rat liver 3 alpha-hydroxysteroid dehydrogenase. Evidence for binary and ternary dead-end complexes containing non-steroidal anti-inflammatory drugs.
1991,
Pubmed
Barski,
Mechanism of human aldehyde reductase: characterization of the active site pocket.
1995,
Pubmed
Castellino,
Time- and voltage-dependent modulation of a Kv1.4 channel by a beta-subunit (Kv beta 3) cloned from ferret ventricle.
1995,
Pubmed
,
Xenbase
Coppock,
Molecular basis of hypoxia-induced pulmonary vasoconstriction: role of voltage-gated K+ channels.
2001,
Pubmed
Grimshaw,
Kinetic and structural effects of activation of bovine kidney aldose reductase.
1989,
Pubmed
Gulbis,
Structure of a voltage-dependent K+ channel beta subunit.
1999,
Pubmed
Gulbis,
Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels.
2000,
Pubmed
,
Xenbase
Haddad,
O2-sensing mechanisms in excitable cells: role of plasma membrane K+ channels.
1997,
Pubmed
Haddad,
Different O2-sensing mechanisms by different K+ channels.
2000,
Pubmed
Heinemann,
Functional characterization of Kv channel beta-subunits from rat brain.
1996,
Pubmed
,
Xenbase
Heinemann,
Molecular and functional characterization of a rat brain Kv beta 3 potassium channel subunit.
1995,
Pubmed
,
Xenbase
Heredia,
Dissection of the physiological interconversion of 5alpha-DHT and 3alpha-diol by rat 3alpha-HSD via transient kinetics shows that the chemical step is rate-determining: effect of mutating cofactor and substrate-binding pocket residues on catalysis.
2004,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Hyndman,
The aldo-keto reductase superfamily homepage.
2003,
Pubmed
Jez,
Characterization of the substrate binding site in rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase. The roles of tryptophans in ligand binding and protein fluorescence.
1996,
Pubmed
Jez,
Comparative anatomy of the aldo-keto reductase superfamily.
1997,
Pubmed
Kubiseski,
Studies on pig muscle aldose reductase. Kinetic mechanism and evidence for a slow conformational change upon coenzyme binding.
1992,
Pubmed
Lee,
Characterization of 4-oxo-2-nonenal as a novel product of lipid peroxidation.
2000,
Pubmed
Liu,
Oxidative stress and potassium channel function.
2002,
Pubmed
Liu,
Binding of pyridine nucleotide coenzymes to the beta-subunit of the voltage-sensitive K+ channel.
2001,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
McCormack,
Shaker K+ channel beta subunits belong to an NAD(P)H-dependent oxidoreductase superfamily.
1994,
Pubmed
Morales,
A novel beta subunit increases rate of inactivation of specific voltage-gated potassium channel alpha subunits.
1995,
Pubmed
,
Xenbase
Parcej,
Oligomeric properties of alpha-dendrotoxin-sensitive potassium ion channels purified from bovine brain.
1992,
Pubmed
Pardo,
Extracellular K+ specifically modulates a rat brain K+ channel.
1992,
Pubmed
,
Xenbase
Patel,
Molecular physiology of oxygen-sensitive potassium channels.
2001,
Pubmed
Penning,
Engineering steroid hormone specificity into aldo-keto reductases.
2001,
Pubmed
Rasmusson,
C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Rettig,
Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
1994,
Pubmed
,
Xenbase
Rindgen,
Covalent modifications to 2'-deoxyguanosine by 4-oxo-2-nonenal, a novel product of lipid peroxidation.
1999,
Pubmed
Rozanski,
A metabolic mechanism for cardiac K+ channel remodelling.
2002,
Pubmed
Ruppersberg,
Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation.
1991,
Pubmed
,
Xenbase
Schlegel,
Mutagenesis of 3 alpha-hydroxysteroid dehydrogenase reveals a "push-pull" mechanism for proton transfer in aldo-keto reductases.
1998,
Pubmed
Schultz,
Localization of two potassium channel beta subunit genes, KCNA1B and KCNA2B.
1996,
Pubmed
Scott,
Primary structure of a beta subunit of alpha-dendrotoxin-sensitive K+ channels from bovine brain.
1994,
Pubmed
Sewing,
Kv beta 1 subunit binding specific for shaker-related potassium channel alpha subunits.
1996,
Pubmed
Shi,
Beta subunits promote K+ channel surface expression through effects early in biosynthesis.
1996,
Pubmed
Tarle,
Probing the active site of human aldose reductase. Site-directed mutagenesis of Asp-43, Tyr-48, Lys-77, and His-110.
1993,
Pubmed
Tseng-Crank,
Functional role of the NH2-terminal cytoplasmic domain of a mammalian A-type K channel.
1993,
Pubmed
,
Xenbase
Weir,
Acute oxygen-sensing mechanisms.
2005,
Pubmed
Yu,
NAB domain is essential for the subunit assembly of both alpha-alpha and alpha-beta complexes of shaker-like potassium channels.
1996,
Pubmed
