Role of the Kv4.3 K
            <sup>+</sup>
            Channel in Ventricular Muscle

Dixon, Jane E.; Shi, Wenmei; Wang, Hong Sheng; McDonald, Christine; Yu, Han-Gang; Wymore, Randy S.; Cohen, Ira S.; McKinnon, David

doi:10.1161/01.res.79.4.659

Cited by 364 publications

(89 citation statements)

References 30 publications

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“…Constructions-Rat Kv4.3 short (14) and long (15) isoform cDNAs were subcloned into pcDNA3 (Invitrogen, Carlsbad CA). Rat Kv2.1, ␤1.1.…”

Section: Methodsmentioning

confidence: 99%

“…Chimeric constructs between Kv4.3 short splicing form and Kv2.1 were made using a two-step overlapped polymerase chain reaction with primers that corresponded to the border region of Kv4.3 and Kv2.1 sequences. Kv4.3-Kv2.1N contains amino acids 1-184 of rat Kv2.1 polypeptide (16) linked to amino acids 183-636 of rat Kv4.3 polypeptide (14). Kv4.3-Kv2.1C consists of amino acids 1-406 of the Kv4.3 polypeptide connected to amino acids 413-853 of the Kv2.1 polypeptide.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Kvβ Subunits Increase Expression of Kv4.3 Channels by Interacting with Their C Termini

Yang

Alvira

Levitan

et al. 2001

Journal of Biological Chemistry

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Auxiliary Kv␤ subunits form complexes with Kv1 family voltage-gated K؉ channels by binding to a part of the N terminus of channel polypeptide. This association influences expression and gating of these channels. Here we show that Kv4.3 proteins are associated with Kv␤2 subunits in the brain. Expression of Kv␤1 or Kv␤2 subunits does not affect Kv4.3 channel gating but increases current density and protein expression. The increase in Kv4.3 protein is larger at longer times after transfection, suggesting that Kv␤-associated channel proteins are more stable than those without the auxiliary subunits. This association between Kv4.3 and Kv␤ subunits requires the C terminus but not the N terminus of the channel polypeptide. Thus, Kv␤ subunits utilize diverse molecular interactions to stimulate the expression of Kv channels from different families.

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“…Constructions-Rat Kv4.3 short (14) and long (15) isoform cDNAs were subcloned into pcDNA3 (Invitrogen, Carlsbad CA). Rat Kv2.1, ␤1.1.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Kvβ Subunits Increase Expression of Kv4.3 Channels by Interacting with Their C Termini

Yang

Alvira

Levitan

et al. 2001

Journal of Biological Chemistry

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“…Rather, these authors most specifically searched for interaction partners with a yeast two hybrid bait corresponding to the cytoplasmic N-terminus (180 amino acids) of the Kv4.3 subtype of Kv4 channels. These channels are related to the Shal gene of Drosophila melanogaster [3,4], and mediate both the subthreshold-activating somatodendritic A-type current (I SA ) in neurons [5,6] and the transient outward current (I to ) in cardiomyocytes [7–9]. The search for Kv4 channel auxiliary β-subunits had been driven by the finding that coexpression of a low molecular weight brain mRNA fraction (2 – 4 kb) caused an increase in surface expression and a modification of the biophysical properties of Shal -related A-type (i.e., rapidly inactivating) channels [10,11], and, in fact, heterologous coexpression of the newly identified KChIPs had very similar effects on Kv4 channels [1].…”

Section: Introductionmentioning

confidence: 99%

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Bähring

2018

Channels

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Kv channel-interacting proteins (KChIPs) belong to the neuronal calcium sensor (NCS) family of Ca2+-binding EF-hand proteins. KChIPs constitute a group of specific auxiliary β-subunits for Kv4 channels, the molecular substrate of transient potassium currents in both neuronal and non-neuronal tissues. Moreover, KChIPs can interact with presenilins to control ER calcium signaling and apoptosis, and with DNA to control gene transcription. Ca2+ binding via their EF-hands, with the consequence of conformational changes, is well documented for KChIPs. Moreover, the Ca2+ dependence of the presenilin/KChIP complex may be related to Alzheimer’s disease and the Ca2+ dependence of the DNA/KChIP complex to pain sensing. However, only in few cases could the Ca2+ binding to KChIPs be directly linked to the control of excitability in nerve and muscle cells known to express Kv4/KChIP channel complexes. This review summarizes current knowledge about the Ca2+ binding properties of KChIPs and the Ca2+ dependencies of macromolecular complexes containing KChIPs, including those with presenilins, DNA and especially Kv4 channels. The respective physiological or pathophysiolgical roles of Ca2+ binding to KChIPs are discussed.

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“…Members of the Shal subfamily of voltage-gated K ϩ (Kv) channel pore-forming (␣) subunits encode rapidly activating and inactivating Kv channels that also recover rapidly from inactivation and are important in the generation of I A channels in neurons (1)(2)(3)(4) and I to channels in cardiac myocytes (5,6). Accumulating evidence suggests that functional Kv4 channels reflect the assembly of Kv4 ␣ subunits with one or more Kv channel accessory subunits and other regulatory proteins that influence channel cell surface expression and/or biophysical properties (7).…”

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confidence: 99%

Co-assembly of Kv4 α Subunits with K+ Channel-interacting Protein 2 Stabilizes Protein Expression and Promotes Surface Retention of Channel Complexes*

Foeger¹,

Marionneau²,

Nerbonne

2010

Journal of Biological Chemistry

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Members of the KMembers of the Shal subfamily of voltage-gated K ϩ (Kv) channel pore-forming (␣) subunits encode rapidly activating and inactivating Kv channels that also recover rapidly from inactivation and are important in the generation of I A channels in neurons (1-4) and I to channels in cardiac myocytes (5, 6). Accumulating evidence suggests that functional Kv4 channels reflect the assembly of Kv4 ␣ subunits with one or more Kv channel accessory subunits and other regulatory proteins that influence channel cell surface expression and/or biophysical properties (7). The K ϩ channel-interacting proteins (KChIP), 4 members of the Neuronal Calcium Sensor superfamily (8, 9), for example, are cytosolic accessory subunits that were initially identified in a yeast two-hybrid screen using the N terminus of Kv4.2 as bait (10). Heterologous co-expression with accessory KChIP subunits increases Kv4.2 current densities, as well as altering the timeand voltage-dependent properties of currents (10 -14). Truncation of the first 40 amino acids in the Kv4.2 N terminus results in the loss of KChIP-mediated current modulation but a paradoxical increase in Kv4.2 current densities (11,14). Progressive truncation of the N terminus (up to 40 amino acids) was reported to result in progressively greater increases in current densities, although it was not determined whether the observed increase reflected increased total and/or cell surface Kv4.2 protein expression. Previous mutagenesis studies have been interpreted as suggesting that the major binding site for KChIP2 on the Kv4.2 N terminus is between residues 11 and 23 (15). Structural analysis of the N terminus of Kv4.3, crystallized in complex with the core region (conserved across all family members) of KChIP1 (16,17), however, revealed that KChIPs bind the distal 20 N-terminal residues of Kv4 ␣ subunits in a hydrophobic binding pocket.The KChIP-mediated increases in Kv4.2 current densities have been ascribed to increased trafficking of channels from the endoplasmic reticulum (ER) to the surface membrane (10,11,18), although a precise motif that regulates ER retention has yet to be identified. The amino acid motif Arg-Xaa-Arg (RXR) has been shown to play a role in ER retention of inwardly rectifying K ϩ channels (Kir) (19). For example, ATP-sensitive K ϩ channels (K ATP ) formed by the co-assembly of Kir6 ␣ subunits and sulfonylurea receptor accessory subunits are retained in the ER when either subunit is expressed alone. Subunit co-assembly, however, masks RXR retention motifs, promoting forward trafficking to the cell surface of channel complexes (20). Although the Kv4.2 N terminus contains (at positions 35-37) an RKR sequence, previous studies suggest that this sequence does not function as an ER retention motif (18). It has also been suggested that Kv4.2 alone traffics out of the ER but fails to progress beyond the Golgi complex in the absence of KChIPs (21 4 The abbreviations used are: KChIP, K ϩ channel-interacting protein; ER, endoplasmic reticulum; HP, holding potentia...

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Role of the Kv4.3 K ⁺ Channel in Ventricular Muscle

Cited by 364 publications

References 30 publications

Kvβ Subunits Increase Expression of Kv4.3 Channels by Interacting with Their C Termini

Kvβ Subunits Increase Expression of Kv4.3 Channels by Interacting with Their C Termini

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Co-assembly of Kv4 α Subunits with K+ Channel-interacting Protein 2 Stabilizes Protein Expression and Promotes Surface Retention of Channel Complexes*

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Role of the Kv4.3 K + Channel in Ventricular Muscle

Cited by 364 publications

References 30 publications

Kvβ Subunits Increase Expression of Kv4.3 Channels by Interacting with Their C Termini

Kvβ Subunits Increase Expression of Kv4.3 Channels by Interacting with Their C Termini

Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Co-assembly of Kv4 α Subunits with K+ Channel-interacting Protein 2 Stabilizes Protein Expression and Promotes Surface Retention of Channel Complexes*

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Role of the Kv4.3 K ⁺ Channel in Ventricular Muscle