Accessory subunit KChIP2 modulates the cardiac L-type calcium current

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Standard

Accessory subunit KChIP2 modulates the cardiac L-type calcium current. / Thomsen, Morten B; Wang, Chaojian; Ozgen, Nazira; Wang, Hong-Gang; Rosen, Michael R; Pitt, Geoffrey S.

I: Circulation Research, Bind 104, Nr. 12, 2009, s. 1382-9.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Thomsen, MB, Wang, C, Ozgen, N, Wang, H-G, Rosen, MR & Pitt, GS 2009, 'Accessory subunit KChIP2 modulates the cardiac L-type calcium current', Circulation Research, bind 104, nr. 12, s. 1382-9. https://doi.org/10.1161/CIRCRESAHA.109.196972

APA

Thomsen, M. B., Wang, C., Ozgen, N., Wang, H-G., Rosen, M. R., & Pitt, G. S. (2009). Accessory subunit KChIP2 modulates the cardiac L-type calcium current. Circulation Research, 104(12), 1382-9. https://doi.org/10.1161/CIRCRESAHA.109.196972

Vancouver

Thomsen MB, Wang C, Ozgen N, Wang H-G, Rosen MR, Pitt GS. Accessory subunit KChIP2 modulates the cardiac L-type calcium current. Circulation Research. 2009;104(12):1382-9. https://doi.org/10.1161/CIRCRESAHA.109.196972

Author

Thomsen, Morten B ; Wang, Chaojian ; Ozgen, Nazira ; Wang, Hong-Gang ; Rosen, Michael R ; Pitt, Geoffrey S. / Accessory subunit KChIP2 modulates the cardiac L-type calcium current. I: Circulation Research. 2009 ; Bind 104, Nr. 12. s. 1382-9.

Bibtex

@article{31e61400368011df8ed1000ea68e967b,
title = "Accessory subunit KChIP2 modulates the cardiac L-type calcium current",
abstract = "Complex modulation of voltage-gated Ca2+ currents through the interplay among Ca2+ channels and various Ca(2+)-binding proteins is increasingly being recognized. The K+ channel interacting protein 2 (KChIP2), originally identified as an auxiliary subunit for K(V)4.2 and a component of the transient outward K+ channel (I(to)), is a Ca(2+)-binding protein whose regulatory functions do not appear restricted to K(V)4.2. Consequently, we hypothesized that KChIP2 is a direct regulator of the cardiac L-type Ca2+ current (I(Ca,L)). We found that I(Ca,L) density from KChIP2(-/-) myocytes is reduced by 28{\%} compared to I(Ca,L) recorded from wild-type myocytes (P<0.05). This reduction in current density results from loss of a direct effect on the Ca2+ channel current, as shown in a transfected cell line devoid of confounding cardiac ion currents. I(Ca,L) regulation by KChIP2 was independent of Ca2+ binding to KChIP2. Biochemical analysis suggested a direct interaction between KChIP2 and the Ca(V)1.2 alpha(1C) subunit N terminus. We found that KChIP2 binds to the N-terminal inhibitory module of alpha(1C) and augments I(Ca,L) current density without increasing Ca(V)1.2 protein expression or trafficking to the plasma membrane. We propose a model in which KChIP2 impedes the N-terminal inhibitory module of Ca(V)1.2, resulting in increased I(Ca,L). In the context of recent reports that KChIP2 modulates multiple K(V) and Na(V) currents, these results suggest that KChIP2 is a multimodal regulator of cardiac ionic currents.",
author = "Thomsen, {Morten B} and Chaojian Wang and Nazira Ozgen and Hong-Gang Wang and Rosen, {Michael R} and Pitt, {Geoffrey S}",
note = "Keywords: Animals; Calcium; Calcium Channels, L-Type; Cell Membrane; Cells, Cultured; Ion Transport; Kv Channel-Interacting Proteins; Male; Membrane Potentials; Mice; Mice, Knockout; Muscle Proteins; Protein Structure, Tertiary; Shal Potassium Channels",
year = "2009",
doi = "10.1161/CIRCRESAHA.109.196972",
language = "English",
volume = "104",
pages = "1382--9",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "AHA/ASA",
number = "12",

}

RIS

TY - JOUR

T1 - Accessory subunit KChIP2 modulates the cardiac L-type calcium current

AU - Thomsen, Morten B

AU - Wang, Chaojian

AU - Ozgen, Nazira

AU - Wang, Hong-Gang

AU - Rosen, Michael R

AU - Pitt, Geoffrey S

N1 - Keywords: Animals; Calcium; Calcium Channels, L-Type; Cell Membrane; Cells, Cultured; Ion Transport; Kv Channel-Interacting Proteins; Male; Membrane Potentials; Mice; Mice, Knockout; Muscle Proteins; Protein Structure, Tertiary; Shal Potassium Channels

PY - 2009

Y1 - 2009

N2 - Complex modulation of voltage-gated Ca2+ currents through the interplay among Ca2+ channels and various Ca(2+)-binding proteins is increasingly being recognized. The K+ channel interacting protein 2 (KChIP2), originally identified as an auxiliary subunit for K(V)4.2 and a component of the transient outward K+ channel (I(to)), is a Ca(2+)-binding protein whose regulatory functions do not appear restricted to K(V)4.2. Consequently, we hypothesized that KChIP2 is a direct regulator of the cardiac L-type Ca2+ current (I(Ca,L)). We found that I(Ca,L) density from KChIP2(-/-) myocytes is reduced by 28% compared to I(Ca,L) recorded from wild-type myocytes (P<0.05). This reduction in current density results from loss of a direct effect on the Ca2+ channel current, as shown in a transfected cell line devoid of confounding cardiac ion currents. I(Ca,L) regulation by KChIP2 was independent of Ca2+ binding to KChIP2. Biochemical analysis suggested a direct interaction between KChIP2 and the Ca(V)1.2 alpha(1C) subunit N terminus. We found that KChIP2 binds to the N-terminal inhibitory module of alpha(1C) and augments I(Ca,L) current density without increasing Ca(V)1.2 protein expression or trafficking to the plasma membrane. We propose a model in which KChIP2 impedes the N-terminal inhibitory module of Ca(V)1.2, resulting in increased I(Ca,L). In the context of recent reports that KChIP2 modulates multiple K(V) and Na(V) currents, these results suggest that KChIP2 is a multimodal regulator of cardiac ionic currents.

AB - Complex modulation of voltage-gated Ca2+ currents through the interplay among Ca2+ channels and various Ca(2+)-binding proteins is increasingly being recognized. The K+ channel interacting protein 2 (KChIP2), originally identified as an auxiliary subunit for K(V)4.2 and a component of the transient outward K+ channel (I(to)), is a Ca(2+)-binding protein whose regulatory functions do not appear restricted to K(V)4.2. Consequently, we hypothesized that KChIP2 is a direct regulator of the cardiac L-type Ca2+ current (I(Ca,L)). We found that I(Ca,L) density from KChIP2(-/-) myocytes is reduced by 28% compared to I(Ca,L) recorded from wild-type myocytes (P<0.05). This reduction in current density results from loss of a direct effect on the Ca2+ channel current, as shown in a transfected cell line devoid of confounding cardiac ion currents. I(Ca,L) regulation by KChIP2 was independent of Ca2+ binding to KChIP2. Biochemical analysis suggested a direct interaction between KChIP2 and the Ca(V)1.2 alpha(1C) subunit N terminus. We found that KChIP2 binds to the N-terminal inhibitory module of alpha(1C) and augments I(Ca,L) current density without increasing Ca(V)1.2 protein expression or trafficking to the plasma membrane. We propose a model in which KChIP2 impedes the N-terminal inhibitory module of Ca(V)1.2, resulting in increased I(Ca,L). In the context of recent reports that KChIP2 modulates multiple K(V) and Na(V) currents, these results suggest that KChIP2 is a multimodal regulator of cardiac ionic currents.

U2 - 10.1161/CIRCRESAHA.109.196972

DO - 10.1161/CIRCRESAHA.109.196972

M3 - Journal article

C2 - 19461043

VL - 104

SP - 1382

EP - 1389

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 12

ER -

ID: 18788896