Research ExplorerPublicationsDPP10 is a new regulator of Nav1.5 channels in human heart

DPP10 is a new regulator of Nav1.5 channels in human heart

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DPP10 is a new regulator of Nav1.5 channels in human heart. / Belau, Fabian; Metzner, Katharina; Christ, Torsten; Ravens, Ursula; Schaefer, Michael; Künzel, Stephan; Li, Wener; Wettwer, Erich; Dobrev, Dobromir; El-Armouche, Ali; Kämmerer, Susanne.

In: INT J CARDIOL, Vol. 284, 01.06.2019, p. 68-73.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Belau, F, Metzner, K, Christ, T, Ravens, U, Schaefer, M, Künzel, S, Li, W, Wettwer, E, Dobrev, D, El-Armouche, A & Kämmerer, S 2019, 'DPP10 is a new regulator of Nav1.5 channels in human heart', INT J CARDIOL, vol. 284, pp. 68-73. https://doi.org/10.1016/j.ijcard.2018.12.072

APA

Belau, F., Metzner, K., Christ, T., Ravens, U., Schaefer, M., Künzel, S., Li, W., Wettwer, E., Dobrev, D., El-Armouche, A., & Kämmerer, S. (2019). DPP10 is a new regulator of Nav1.5 channels in human heart. INT J CARDIOL, 284, 68-73. https://doi.org/10.1016/j.ijcard.2018.12.072

Vancouver

Belau F, Metzner K, Christ T, Ravens U, Schaefer M, Künzel S et al. DPP10 is a new regulator of Nav1.5 channels in human heart. INT J CARDIOL. 2019 Jun 1;284:68-73. https://doi.org/10.1016/j.ijcard.2018.12.072

Bibtex

@article{17e97a6f9aaf40a1ac5de474db76e9fb,
title = "DPP10 is a new regulator of Nav1.5 channels in human heart",
abstract = "BACKGROUND: Cardiac accessory β-subunits are part of macromolecular Nav1.5 channel complexes modulating biophysical properties and contributing to arrhythmias. Recent studies demonstrated the structural interaction between β-subunits of Na+ (Nav1.5) and K+ (Kv4.3) channels. Here, we identified the dipeptidyl peptidase-like protein-10 (DPP10), which is known to modulate Kv4.3-current kinetics, as a new regulator of Nav1.5 channels.METHODS: We assessed DPP10 expression in the healthy and diseased human heart and we studied the functional effects of DPP10 on the Na+ current in isolated rat cardiomyocytes expressing DPP10 after adenoviral gene-transfer (DPP10ad).RESULTS: DPP10 mRNA and proteins were detected in human ventricle, with higher levels in patients with heart failure. In rat cardiomyocytes, DPP10ad significantly reduced upstroke velocity of action potentials indicating reduction in Na+-current density. DPP10 significantly shifted the voltage-dependent Na+ channel activation and inactivation curve to more positive potentials, resulting in greater availability of Na+ channels for activation, along with increasing window Na+ current. In addition, time-to-peak Na+ current was reduced, whereas time course of recovery from inactivation was significantly accelerated by DPP10ad. DPP10 co-immunoprecipitated with Nav1.5 channels in human ventricles, confirming their physical interaction.CONCLUSION: We provide first evidence that DPP10 interacts with Nav1.5 channels, linking Na+- and K+-channel complexes in the heart. Our data suggest that increased ventricular DPP10 expression in heart failure might promote arrhythmias by decreasing peak Na+ current, while increasing window Na+ current and channel re-openings due to accelerated recovery from inactivation.",
keywords = "Animals, Arrhythmias, Cardiac/genetics, Cell Line, Cricetinae, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/biosynthesis, Disease Models, Animal, Female, Gene Expression Regulation, Humans, Male, Myocardium/metabolism, NAV1.5 Voltage-Gated Sodium Channel/metabolism, RNA/genetics, Rats, Rats, Wistar",
author = "Fabian Belau and Katharina Metzner and Torsten Christ and Ursula Ravens and Michael Schaefer and Stephan K{\"u}nzel and Wener Li and Erich Wettwer and Dobromir Dobrev and Ali El-Armouche and Susanne K{\"a}mmerer",
note = "Copyright {\textcopyright} 2019 Elsevier B.V. All rights reserved.",
year = "2019",
month = jun,
day = "1",
doi = "10.1016/j.ijcard.2018.12.072",
language = "English",
volume = "284",
pages = "68--73",
journal = "INT J CARDIOL",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - DPP10 is a new regulator of Nav1.5 channels in human heart

AU - Belau, Fabian

AU - Metzner, Katharina

AU - Christ, Torsten

AU - Ravens, Ursula

AU - Schaefer, Michael

AU - Künzel, Stephan

AU - Li, Wener

AU - Wettwer, Erich

AU - Dobrev, Dobromir

AU - El-Armouche, Ali

AU - Kämmerer, Susanne

N1 - Copyright © 2019 Elsevier B.V. All rights reserved.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - BACKGROUND: Cardiac accessory β-subunits are part of macromolecular Nav1.5 channel complexes modulating biophysical properties and contributing to arrhythmias. Recent studies demonstrated the structural interaction between β-subunits of Na+ (Nav1.5) and K+ (Kv4.3) channels. Here, we identified the dipeptidyl peptidase-like protein-10 (DPP10), which is known to modulate Kv4.3-current kinetics, as a new regulator of Nav1.5 channels.METHODS: We assessed DPP10 expression in the healthy and diseased human heart and we studied the functional effects of DPP10 on the Na+ current in isolated rat cardiomyocytes expressing DPP10 after adenoviral gene-transfer (DPP10ad).RESULTS: DPP10 mRNA and proteins were detected in human ventricle, with higher levels in patients with heart failure. In rat cardiomyocytes, DPP10ad significantly reduced upstroke velocity of action potentials indicating reduction in Na+-current density. DPP10 significantly shifted the voltage-dependent Na+ channel activation and inactivation curve to more positive potentials, resulting in greater availability of Na+ channels for activation, along with increasing window Na+ current. In addition, time-to-peak Na+ current was reduced, whereas time course of recovery from inactivation was significantly accelerated by DPP10ad. DPP10 co-immunoprecipitated with Nav1.5 channels in human ventricles, confirming their physical interaction.CONCLUSION: We provide first evidence that DPP10 interacts with Nav1.5 channels, linking Na+- and K+-channel complexes in the heart. Our data suggest that increased ventricular DPP10 expression in heart failure might promote arrhythmias by decreasing peak Na+ current, while increasing window Na+ current and channel re-openings due to accelerated recovery from inactivation.

AB - BACKGROUND: Cardiac accessory β-subunits are part of macromolecular Nav1.5 channel complexes modulating biophysical properties and contributing to arrhythmias. Recent studies demonstrated the structural interaction between β-subunits of Na+ (Nav1.5) and K+ (Kv4.3) channels. Here, we identified the dipeptidyl peptidase-like protein-10 (DPP10), which is known to modulate Kv4.3-current kinetics, as a new regulator of Nav1.5 channels.METHODS: We assessed DPP10 expression in the healthy and diseased human heart and we studied the functional effects of DPP10 on the Na+ current in isolated rat cardiomyocytes expressing DPP10 after adenoviral gene-transfer (DPP10ad).RESULTS: DPP10 mRNA and proteins were detected in human ventricle, with higher levels in patients with heart failure. In rat cardiomyocytes, DPP10ad significantly reduced upstroke velocity of action potentials indicating reduction in Na+-current density. DPP10 significantly shifted the voltage-dependent Na+ channel activation and inactivation curve to more positive potentials, resulting in greater availability of Na+ channels for activation, along with increasing window Na+ current. In addition, time-to-peak Na+ current was reduced, whereas time course of recovery from inactivation was significantly accelerated by DPP10ad. DPP10 co-immunoprecipitated with Nav1.5 channels in human ventricles, confirming their physical interaction.CONCLUSION: We provide first evidence that DPP10 interacts with Nav1.5 channels, linking Na+- and K+-channel complexes in the heart. Our data suggest that increased ventricular DPP10 expression in heart failure might promote arrhythmias by decreasing peak Na+ current, while increasing window Na+ current and channel re-openings due to accelerated recovery from inactivation.

KW - Animals

KW - Arrhythmias, Cardiac/genetics

KW - Cell Line

KW - Cricetinae

KW - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/biosynthesis

KW - Disease Models, Animal

KW - Female

KW - Gene Expression Regulation

KW - Humans

KW - Male

KW - Myocardium/metabolism

KW - NAV1.5 Voltage-Gated Sodium Channel/metabolism

KW - RNA/genetics

KW - Rats

KW - Rats, Wistar

U2 - 10.1016/j.ijcard.2018.12.072

DO - 10.1016/j.ijcard.2018.12.072

M3 - SCORING: Journal article

C2 - 30638748

VL - 284

SP - 68

EP - 73

JO - INT J CARDIOL

JF - INT J CARDIOL

SN - 0167-5273

ER -