Channelpedia

Kcnab1

Description: potassium voltage-gated channel, shaker-related subfamily, beta member 1
Gene: Kcnab1     Synonyms: kcnab1

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Introduction

This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member includes three distinct isoforms which are encoded by three alternatively spliced transcript variants of this gene. These three isoforms are beta subunits, which form heteromultimeric complex with alpha subunits and modulate the activity of the pore-forming alpha subunits. he Shaker family voltage-dependent potassium channels (Kv1) assemble with cytosolic beta-subunits (Kvbeta) to form a stable complex.


Experimental data


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Gene

RGD ID Chromosome Position Species
61827 2 154837841-155145882 Rat
62118 3 64913565-65182141 Mouse
1607081 3 155838337-156256927 Human

Kcnab1 : potassium voltage-gated channel, shaker-related subfamily, beta member 1


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Transcript

Acc No Sequence Length Source
NM_017303 n/A n/A NCBI
NM_010597 n/A n/A NCBI
NM_003471 n/A n/A NCBI
NM_172159 n/A n/A NCBI
NM_172160 n/A n/A NCBI

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Ontology

Accession Name Definition Evidence
GO:0016021 integral to membrane Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane. IEA
GO:0005737 cytoplasm All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. IEA

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Interaction

Voltage-activated potassium (Kv) channels from mammalian brain are hetero-oligomers containing alpha and beta subunits. Coexpression of Kv1 alpha and Kv beta 1 subunits confers rapid A-type inactivation on noninactivating potassium channels (delayed rectifiers) in expression systems in vitro. 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.


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Protein


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Structure

In contrast to previous studies using K+ channel alpha subunits, peptides based on the N-terminal of the Kv-beta-1 subunit were unable to mimic the action of the entire subunit. This indicates differences between the inactivation induced by the Kv-beta-1 subunit and the N-type inactivation mechanism associated with certain rapidly-inactivating cloned K+ channel alpha subunits [305].


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Distribution


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Expression

Four different Kvb subunits have been identified which are uniquely expressed in lymphocytes, brain and heart [572].

The expression of the three Kvbeta isoforms in the rat CNS depends on its age. Kvb expression is restricted to the spinal cord and dorsal root ganglia in the embryonic CNS. At birth, Kvb expression is detected in brainstem and midbrain nuclei, but was not detected in the hippocampus, cerebellum or cerebral cortex. During the first postnatal week, Kvb expression is present in hippocampal and cortical pyramidal cells and in cerebellar Purkinje cells. Expression of Kvb subunits reaches adult levels by the third postnatal week in all of the brain regions examined. Kvb1 expression is high at birth in all brain regions examined and decreases with age. In contrast, Kvb2 expression is low at birth and increases with age to reach adult levels by the third postnatal week [310].


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Functional


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Kinetics

The coexpression of the rat KvlB1 subunit with the mouse Kvl.1 (mKvl.1) K+ channel in Chinese hamster ovary cells caused an increase in the rate of inactivation of whole-cell current. Current decayed in a bi-exponential fashion with a fast voltage-dependent and a slower voltage-independent component. The inactivating current component accounted for around 40% of the total outward current [305].


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Model


References

306

Pan Y. et al. Functional coupling between the Kv1.1 channel and aldoketoreductase Kvbeta1.
J. Biol. Chem., 2008 Mar 28 , 283 (8634-42).

310

Downen M. et al. Developmental expression of voltage-gated potassium channel beta subunits.
Brain Res. Dev. Brain Res., 1999 Oct 20 , 117 (71-80).

572

Jan YN. et al. Cloned potassium channels from eukaryotes and prokaryotes.
Annu. Rev. Neurosci., 1997 , 20 (91-123).


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Credits

Editor : Admin.

Contributors : Rajnish Ranjan, Michael Schartner

To cite : [Editor], [Contributors]. Accessed on [Date] Channelpedia , http://channelpedia.epfl.ch/ionchannels/145