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

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Pages (from-to)68-73
Number of pages6
JournalInternational journal of cardiology
Publication statusPublished - 1 Jun 2019

External IDs

Scopus 85059672459
ORCID /0009-0008-1895-4538/work/142248973
ORCID /0000-0003-2514-9429/work/148606789


Sustainable Development Goals


  • 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