Molecular cloning and functional expression of the K+ channel KV7.1 and the regulatory subunit KCNE1 from equine myocardium

Philip Juul Pedersen; Kirsten B. Thomsen; Jon B. Flak; Maria de los Angeles Tejada; Frank Hauser; Dagmar Senta Trachsel; Rikke Buhl; Theodore Kalbfleisch; Michael Scott DePriest; James N. MacLeod; Kirstine Callø; Dan Arne Klærke

doi:10.1016/j.rvsc.2017.09.010

Molecular cloning and functional expression of the K⁺ channel K_V7.1 and the regulatory subunit KCNE1 from equine myocardium

Philip Juul Pedersen, Kirsten B. Thomsen, Jon B. Flak, Maria de los Angeles Tejada, Frank Hauser, Dagmar Senta Trachsel, Rikke Buhl, Theodore Kalbfleisch, Michael Scott DePriest, James N. MacLeod, Kirstine Callø^*, Dan Arne Klærke

^*Corresponding author for this work

1 Citation (Scopus)

Abstract

Background The voltage-gated K⁺-channel K_V7.1 and the subunit KCNE1, encoded by the KCNQ1 and KCNE1 genes, respectively, are responsible for termination of the cardiac action potential. In humans, mutations in these genes can predispose patients to arrhythmias and sudden cardiac death (SCD). Aim To characterize equine K_V7.1/KCNE1 currents and compare them to human K_V7.1/KCNE1 currents to determine whether K_V7.1/KCNE1 plays a similar role in equine and human hearts. Methods mRNA encoding K_V7.1 and KCNE1 was isolated from equine hearts, sequenced, and cloned into expression vectors. The channel subunits were heterologously expressed in Xenopus laevis oocytes or CHO-K1 cells and characterized using voltage-clamp techniques. Results Equine K_V7.1/KCNE1 expressed in CHO-K1 cells exhibited electrophysiological properties that are overall similar to the human orthologs; however, a slower deactivation was found which could result in more open channels at fast rates. Conclusion The results suggest that the equine K_V7.1/KCNE1 channel may be important for cardiac repolarization and this could indicate that horses are susceptible to SCD caused by mutations in KCNQ1 and KCNE1.

Original language	English
Journal	Research in Veterinary Science
Volume	113
Pages (from-to)	79-86
Number of pages	8
ISSN	0034-5288
DOIs	https://doi.org/10.1016/j.rvsc.2017.09.010 https://doi.org/10.1016/j.rvsc.2017.12.014
Publication status	Published - Aug 2017

Keywords

Cardiac electrophysiology
Equine
Horse
K7.1
KCNE1
KCNQ1

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10.1016/j.rvsc.2017.09.010
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Pedersen, P. J., Thomsen, K. B., Flak, J. B., Tejada, M. D. L. A., Hauser, F., Trachsel, D. S., Buhl, R., Kalbfleisch, T., DePriest, M. S., MacLeod, J. N., Callø, K., & Klærke, D. A. (2017). Molecular cloning and functional expression of the K⁺ channel K_V7.1 and the regulatory subunit KCNE1 from equine myocardium. Research in Veterinary Science, 113, 79-86. https://doi.org/10.1016/j.rvsc.2017.09.010, https://doi.org/10.1016/j.rvsc.2017.12.014

Pedersen, PJ, Thomsen, KB, Flak, JB, Tejada, MDLA , Hauser, F, Trachsel, DS, Buhl, R, Kalbfleisch, T, DePriest, MS, MacLeod, JN, Callø, K & Klærke, DA 2017, 'Molecular cloning and functional expression of the K⁺ channel K_V7.1 and the regulatory subunit KCNE1 from equine myocardium', Research in Veterinary Science, vol. 113, pp. 79-86. https://doi.org/10.1016/j.rvsc.2017.09.010, https://doi.org/10.1016/j.rvsc.2017.12.014

@article{2a7206cbf38349968cc348c530fafa57,

title = "Molecular cloning and functional expression of the K+ channel KV7.1 and the regulatory subunit KCNE1 from equine myocardium",

abstract = "Background The voltage-gated K+-channel KV7.1 and the subunit KCNE1, encoded by the KCNQ1 and KCNE1 genes, respectively, are responsible for termination of the cardiac action potential. In humans, mutations in these genes can predispose patients to arrhythmias and sudden cardiac death (SCD). Aim To characterize equine KV7.1/KCNE1 currents and compare them to human KV7.1/KCNE1 currents to determine whether KV7.1/KCNE1 plays a similar role in equine and human hearts. Methods mRNA encoding KV7.1 and KCNE1 was isolated from equine hearts, sequenced, and cloned into expression vectors. The channel subunits were heterologously expressed in Xenopus laevis oocytes or CHO-K1 cells and characterized using voltage-clamp techniques. Results Equine KV7.1/KCNE1 expressed in CHO-K1 cells exhibited electrophysiological properties that are overall similar to the human orthologs; however, a slower deactivation was found which could result in more open channels at fast rates. Conclusion The results suggest that the equine KV7.1/KCNE1 channel may be important for cardiac repolarization and this could indicate that horses are susceptible to SCD caused by mutations in KCNQ1 and KCNE1.",

keywords = "Cardiac electrophysiology, Equine, Horse, K7.1, KCNE1, KCNQ1",

author = "Pedersen, {Philip Juul} and Thomsen, {Kirsten B.} and Flak, {Jon B.} and Tejada, {Maria de los Angeles} and Frank Hauser and Trachsel, {Dagmar Senta} and Rikke Buhl and Theodore Kalbfleisch and DePriest, {Michael Scott} and MacLeod, {James N.} and Kirstine Call{\o} and Kl{\ae}rke, {Dan Arne}",

note = "Corrigendum to {"}Molecular cloning and functional expression of the K+ channel KV7.1 and the regulatory subunit KCNE1 from equine myocardium{"} [Res. Vet. Sci. 113 (2017) 79-86]",

year = "2017",

month = aug,

doi = "10.1016/j.rvsc.2017.09.010",

language = "English",

volume = "113",

pages = "79--86",

journal = "Research in Veterinary Science",

issn = "0034-5288",

publisher = "Elsevier",

}

TY - JOUR

T1 - Molecular cloning and functional expression of the K+ channel KV7.1 and the regulatory subunit KCNE1 from equine myocardium

AU - Pedersen, Philip Juul

AU - Thomsen, Kirsten B.

AU - Flak, Jon B.

AU - Tejada, Maria de los Angeles

AU - Hauser, Frank

AU - Trachsel, Dagmar Senta

AU - Buhl, Rikke

AU - Kalbfleisch, Theodore

AU - DePriest, Michael Scott

AU - MacLeod, James N.

AU - Callø, Kirstine

AU - Klærke, Dan Arne

N1 - Corrigendum to "Molecular cloning and functional expression of the K+ channel KV7.1 and the regulatory subunit KCNE1 from equine myocardium" [Res. Vet. Sci. 113 (2017) 79-86]

PY - 2017/8

Y1 - 2017/8

N2 - Background The voltage-gated K+-channel KV7.1 and the subunit KCNE1, encoded by the KCNQ1 and KCNE1 genes, respectively, are responsible for termination of the cardiac action potential. In humans, mutations in these genes can predispose patients to arrhythmias and sudden cardiac death (SCD). Aim To characterize equine KV7.1/KCNE1 currents and compare them to human KV7.1/KCNE1 currents to determine whether KV7.1/KCNE1 plays a similar role in equine and human hearts. Methods mRNA encoding KV7.1 and KCNE1 was isolated from equine hearts, sequenced, and cloned into expression vectors. The channel subunits were heterologously expressed in Xenopus laevis oocytes or CHO-K1 cells and characterized using voltage-clamp techniques. Results Equine KV7.1/KCNE1 expressed in CHO-K1 cells exhibited electrophysiological properties that are overall similar to the human orthologs; however, a slower deactivation was found which could result in more open channels at fast rates. Conclusion The results suggest that the equine KV7.1/KCNE1 channel may be important for cardiac repolarization and this could indicate that horses are susceptible to SCD caused by mutations in KCNQ1 and KCNE1.

AB - Background The voltage-gated K+-channel KV7.1 and the subunit KCNE1, encoded by the KCNQ1 and KCNE1 genes, respectively, are responsible for termination of the cardiac action potential. In humans, mutations in these genes can predispose patients to arrhythmias and sudden cardiac death (SCD). Aim To characterize equine KV7.1/KCNE1 currents and compare them to human KV7.1/KCNE1 currents to determine whether KV7.1/KCNE1 plays a similar role in equine and human hearts. Methods mRNA encoding KV7.1 and KCNE1 was isolated from equine hearts, sequenced, and cloned into expression vectors. The channel subunits were heterologously expressed in Xenopus laevis oocytes or CHO-K1 cells and characterized using voltage-clamp techniques. Results Equine KV7.1/KCNE1 expressed in CHO-K1 cells exhibited electrophysiological properties that are overall similar to the human orthologs; however, a slower deactivation was found which could result in more open channels at fast rates. Conclusion The results suggest that the equine KV7.1/KCNE1 channel may be important for cardiac repolarization and this could indicate that horses are susceptible to SCD caused by mutations in KCNQ1 and KCNE1.

KW - Cardiac electrophysiology

KW - Equine

KW - Horse

KW - K7.1

KW - KCNE1

KW - KCNQ1

UR - https://www.sciencedirect.com/science/article/pii/S0034528817312845?via%3Dihub

U2 - 10.1016/j.rvsc.2017.09.010

DO - 10.1016/j.rvsc.2017.09.010

M3 - Journal article

C2 - 28917093

AN - SCOPUS:85029361238

SN - 0034-5288

VL - 113

SP - 79

EP - 86

JO - Research in Veterinary Science

JF - Research in Veterinary Science

ER -

Molecular cloning and functional expression of the K⁺ channel K_V7.1 and the regulatory subunit KCNE1 from equine myocardium

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