Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle

Research output: Contribution to journalJournal articlepeer-review

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Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle. / Calloe, Kirstine; Soltysinska, Ewa; Jespersen, Thomas; Lundby, Alicia; Antzelevitch, Charles; Olesen, Søren-Peter; Cordeiro, Jonathan M.

In: Journal of Molecular and Cellular Cardiology, Vol. 48, No. 1, 2009, p. 191-200.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Calloe, K, Soltysinska, E, Jespersen, T, Lundby, A, Antzelevitch, C, Olesen, S-P & Cordeiro, JM 2009, 'Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle', Journal of Molecular and Cellular Cardiology, vol. 48, no. 1, pp. 191-200. https://doi.org/10.1016/j.yjmcc.2009.07.017

APA

Calloe, K., Soltysinska, E., Jespersen, T., Lundby, A., Antzelevitch, C., Olesen, S-P., & Cordeiro, J. M. (2009). Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle. Journal of Molecular and Cellular Cardiology, 48(1), 191-200. https://doi.org/10.1016/j.yjmcc.2009.07.017

Vancouver

Calloe K, Soltysinska E, Jespersen T, Lundby A, Antzelevitch C, Olesen S-P et al. Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle. Journal of Molecular and Cellular Cardiology. 2009;48(1):191-200. https://doi.org/10.1016/j.yjmcc.2009.07.017

Author

Calloe, Kirstine ; Soltysinska, Ewa ; Jespersen, Thomas ; Lundby, Alicia ; Antzelevitch, Charles ; Olesen, Søren-Peter ; Cordeiro, Jonathan M. / Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle. In: Journal of Molecular and Cellular Cardiology. 2009 ; Vol. 48, No. 1. pp. 191-200.

Bibtex

@article{a2c0d6a0333e11df8ed1000ea68e967b,
title = "Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle",
abstract = "To examine the electrophysiological and molecular properties of the transient outward current (I(to)) in canine left ventricle using a novel I(to) activator, NS5806, I(to) was measured in isolated epicardial (Epi), midmyocardial (Mid) and endocardial (Endo) cells using whole-cell patch-clamp techniques. NS5806 activation of K(v)4.3 current was also studied in CHO-K1 cells and Xenopus laevis oocytes. In CHO-K1 cells co-transfected with K(v)4.3 and KChIP2, NS5806 (10 microM) caused a 35% increase in current amplitude and a marked slowing of current decay with tau increasing from 7.0+/-0.4 to 10.2+/-0.3 ms. In the absence of KChIP2, current decay was unaffected by NS5806. In ventricular myocytes, NS5806 increased I(to) density by 80%, 82%, and 16% in Epi, Mid, and Endo myocytes, respectively (at +40 mV) and shifted steady-state inactivation to negative potentials. NS5806 also significantly slowed decay of I(to), increasing total charge to 227%, 192% and 83% of control in Epi, Mid and Endo cells, respectively (+40 mV, p<0.05). Quantification of K(v)4.3 and KChIP2 mRNA in the 3 ventricular cell types revealed that levels of K(v)4.3 message was uniform but those of KChIP2 were significantly greater in Epi and Mid cells. The KChIP2 gradient was confirmed at the protein level by Western blot. Our results suggest that NS5806 augments I(to) by increasing current density and slowing decay and that both depend on the presence of KChIP2. I(to) and its augmentation by NS5806 are greatest in Epi and Mid cells because KChIP2 levels are highest in these cell types.",
author = "Kirstine Calloe and Ewa Soltysinska and Thomas Jespersen and Alicia Lundby and Charles Antzelevitch and S{\o}ren-Peter Olesen and Cordeiro, {Jonathan M}",
note = "Copyright 2009 Elsevier Inc. All rights reserved.",
year = "2009",
doi = "10.1016/j.yjmcc.2009.07.017",
language = "English",
volume = "48",
pages = "191--200",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press",
number = "1",

}

RIS

TY - JOUR

T1 - Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle

AU - Calloe, Kirstine

AU - Soltysinska, Ewa

AU - Jespersen, Thomas

AU - Lundby, Alicia

AU - Antzelevitch, Charles

AU - Olesen, Søren-Peter

AU - Cordeiro, Jonathan M

N1 - Copyright 2009 Elsevier Inc. All rights reserved.

PY - 2009

Y1 - 2009

N2 - To examine the electrophysiological and molecular properties of the transient outward current (I(to)) in canine left ventricle using a novel I(to) activator, NS5806, I(to) was measured in isolated epicardial (Epi), midmyocardial (Mid) and endocardial (Endo) cells using whole-cell patch-clamp techniques. NS5806 activation of K(v)4.3 current was also studied in CHO-K1 cells and Xenopus laevis oocytes. In CHO-K1 cells co-transfected with K(v)4.3 and KChIP2, NS5806 (10 microM) caused a 35% increase in current amplitude and a marked slowing of current decay with tau increasing from 7.0+/-0.4 to 10.2+/-0.3 ms. In the absence of KChIP2, current decay was unaffected by NS5806. In ventricular myocytes, NS5806 increased I(to) density by 80%, 82%, and 16% in Epi, Mid, and Endo myocytes, respectively (at +40 mV) and shifted steady-state inactivation to negative potentials. NS5806 also significantly slowed decay of I(to), increasing total charge to 227%, 192% and 83% of control in Epi, Mid and Endo cells, respectively (+40 mV, p<0.05). Quantification of K(v)4.3 and KChIP2 mRNA in the 3 ventricular cell types revealed that levels of K(v)4.3 message was uniform but those of KChIP2 were significantly greater in Epi and Mid cells. The KChIP2 gradient was confirmed at the protein level by Western blot. Our results suggest that NS5806 augments I(to) by increasing current density and slowing decay and that both depend on the presence of KChIP2. I(to) and its augmentation by NS5806 are greatest in Epi and Mid cells because KChIP2 levels are highest in these cell types.

AB - To examine the electrophysiological and molecular properties of the transient outward current (I(to)) in canine left ventricle using a novel I(to) activator, NS5806, I(to) was measured in isolated epicardial (Epi), midmyocardial (Mid) and endocardial (Endo) cells using whole-cell patch-clamp techniques. NS5806 activation of K(v)4.3 current was also studied in CHO-K1 cells and Xenopus laevis oocytes. In CHO-K1 cells co-transfected with K(v)4.3 and KChIP2, NS5806 (10 microM) caused a 35% increase in current amplitude and a marked slowing of current decay with tau increasing from 7.0+/-0.4 to 10.2+/-0.3 ms. In the absence of KChIP2, current decay was unaffected by NS5806. In ventricular myocytes, NS5806 increased I(to) density by 80%, 82%, and 16% in Epi, Mid, and Endo myocytes, respectively (at +40 mV) and shifted steady-state inactivation to negative potentials. NS5806 also significantly slowed decay of I(to), increasing total charge to 227%, 192% and 83% of control in Epi, Mid and Endo cells, respectively (+40 mV, p<0.05). Quantification of K(v)4.3 and KChIP2 mRNA in the 3 ventricular cell types revealed that levels of K(v)4.3 message was uniform but those of KChIP2 were significantly greater in Epi and Mid cells. The KChIP2 gradient was confirmed at the protein level by Western blot. Our results suggest that NS5806 augments I(to) by increasing current density and slowing decay and that both depend on the presence of KChIP2. I(to) and its augmentation by NS5806 are greatest in Epi and Mid cells because KChIP2 levels are highest in these cell types.

U2 - 10.1016/j.yjmcc.2009.07.017

DO - 10.1016/j.yjmcc.2009.07.017

M3 - Journal article

C2 - 19632239

VL - 48

SP - 191

EP - 200

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 1

ER -

ID: 18699112