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J Biol Chem
2008 Mar 28;28313:8634-42. doi: 10.1074/jbc.M709304200.
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Functional coupling between the Kv1.1 channel and aldoketoreductase Kvbeta1.
Pan Y
,
Weng J
,
Cao Y
,
Bhosle RC
,
Zhou M
.
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The Shaker family voltage-dependent potassium channels (Kv1) assemble with cytosolic beta-subunits (Kvbeta) to form a stable complex. All Kvbeta subunits have a conserved core domain, which in one of them (Kvbeta2) is an aldoketoreductase that utilizes NADPH as a cofactor. In addition to this core, Kvbeta1 has an N terminus that closes the channel by the N-type inactivation mechanism. Point mutations in the putative catalytic site of Kvbeta1 alter the on-rate of inactivation. Whether the core of Kvbeta1 functions as an enzyme and whether its enzymatic activity affects N-type inactivation had not been explored. Here, we show that Kvbeta1 is a functional aldoketoreductase and that oxidation of the Kvbeta1-bound cofactor, either enzymatically by a substrate or non-enzymatically by hydrogen peroxide or NADP(+), induces a large increase in open channel current. The modulation is not affected by deletion of the distal C terminus of the channel, which has been suggested in structural studies to interact with Kvbeta. The rate of increase in current, which reflects NADPH oxidation, is approximately 2-fold faster at 0-mV membrane potential than at -100 mV. Thus, cofactor oxidation by Kvbeta1 is regulated by membrane potential, presumably via voltage-dependent structural changes in Kv1.1 channels.
Adelman,
Episodic ataxia results from voltage-dependent potassium channels with altered functions.
1995, Pubmed,
Xenbase
Adelman,
Episodic ataxia results from voltage-dependent potassium channels with altered functions.
1995,
Pubmed
,
Xenbase
Aldrich,
Mechanism of frequency-dependent broadening of molluscan neurone soma spikes.
1979,
Pubmed
Bähring,
Coupling of voltage-dependent potassium channel inactivation and oxidoreductase active site of Kvbeta subunits.
2001,
Pubmed
,
Xenbase
Cahalan,
Molecular properties and physiological roles of ion channels in the immune system.
2001,
Pubmed
Ciorba,
Modulation of potassium channel function by methionine oxidation and reduction.
1997,
Pubmed
,
Xenbase
Ciorba,
Regulation of voltage-dependent K+ channels by methionine oxidation: effect of nitric oxide and vitamin C.
1999,
Pubmed
,
Xenbase
Connor,
Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma.
1971,
Pubmed
Gu,
A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channels.
2003,
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
Heilstedt,
Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome.
2001,
Pubmed
Heinemann,
Molecular and functional characterization of a rat brain Kv beta 3 potassium channel subunit.
1995,
Pubmed
,
Xenbase
Hoshi,
Regulation of cell function by methionine oxidation and reduction.
2001,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Lee,
Characterization of 4-oxo-2-nonenal as a novel product of lipid peroxidation.
2000,
Pubmed
Lee,
Adult alveolar epithelial cells express multiple subtypes of voltage-gated K+ channels that are located in apical membrane.
2003,
Pubmed
Lewis,
Potassium and calcium channels in lymphocytes.
1995,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
MacKinnon,
Determination of the subunit stoichiometry of a voltage-activated potassium channel.
1991,
Pubmed
,
Xenbase
McCormack,
Shaker K+ channel beta subunits belong to an NAD(P)H-dependent oxidoreductase superfamily.
1994,
Pubmed
Murata,
Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
2005,
Pubmed
,
Xenbase
Nagaya,
Potassium channel alpha and beta subunits assemble in the endoplasmic reticulum.
1997,
Pubmed
Nerbonne,
Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium.
2000,
Pubmed
Parcej,
Structural characterisation of neuronal voltage-sensitive K+ channels heterologously expressed in Pichia pastoris.
2003,
Pubmed
Pongs,
Functional and molecular aspects of voltage-gated K+ channel beta subunits.
1999,
Pubmed
,
Xenbase
Rettig,
Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
1994,
Pubmed
,
Xenbase
Rhodes,
Association and colocalization of K+ channel alpha- and beta-subunit polypeptides in rat brain.
1995,
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
Scott,
Primary structure of a beta subunit of alpha-dendrotoxin-sensitive K+ channels from bovine brain.
1994,
Pubmed
Sokolova,
Conformational changes in the C terminus of Shaker K+ channel bound to the rat Kvbeta2-subunit.
2003,
Pubmed
Tipparaju,
Differential regulation of voltage-gated K+ channels by oxidized and reduced pyridine nucleotide coenzymes.
2005,
Pubmed
Trimmer,
Localization of voltage-gated ion channels in mammalian brain.
2004,
Pubmed
Veal,
Hydrogen peroxide sensing and signaling.
2007,
Pubmed
Wallner,
Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog.
1999,
Pubmed
,
Xenbase
Weng,
Modulation of voltage-dependent Shaker family potassium channels by an aldo-keto reductase.
2006,
Pubmed
,
Xenbase
Xia,
Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells.
1999,
Pubmed
,
Xenbase
Zagotta,
Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.
1990,
Pubmed
,
Xenbase
