Abstract
Abstract 14053: Sumoylation of the Cardiac Sodium Channel Na V 1.5 Does Not Increase Late Sodium Current
Circulation (New York, N.Y.), Vol.144(Suppl_1)
11/16/2021
DOI: 10.1161/circ.144.suppl_1.14053
Abstract
Introduction:
The sodium current (I
Na
) controlling cardiac cell excitability is conducted via the Na
+
channel Na
V
1.5 (encoded by
SCN5A
). Dysregulation of Na
V
1.5 has been implicated in arrhythmia, with increased late Na
V
1.5 current (I
Na,L
) causing long QT type 3. Many Na
V
1.5 post-translational modifications have been reported by us and others, including SUMOylation, the addition of a Small Ubiquitin-like MOdifier (SUMO) at K442-Na
V
1.5. Plant et al. (2020) recently reported that hypoxia increases I
Na,L
by increased Na
V
1.5 SUMOylation.
Hypothesis:
SUMOylation modifies peak but not late Na
V
1.5 currents through membrane localization.
Methods:
SUMOylation of Na
V
1.5 by SUMO1 was detected by immunoprecipitation and immunoblot. The effects of SUMOylation on peak I
Na
and I
Na,L
were measured using patch clamp in HEK293 cells transfected with wild type (WT) or mutant K442R-Na
V
1.5 with/without the β1 subunit and in neonatal rat cardiac myocytes (NRCMs). Tetrodotoxin (TTX) was used to quantitate I
Na,L
in NRCMs. Na
V
1.5 trafficking was detected by immunofluorescence.
Results:
Na
V
1.5 was SUMOylated by SUMO1 in HEK cells, NRCMs, and human heart samples. Overexpressing or directly applying SUMO1 induced hyperSUMOylation of Na
V
1.5 at K442 and increased the amplitude of peak I
Na
in NRCMs and in HEK cells overexpressing WT but not K442R-Na
v
1.5. SUMOylation did not affect I
Na,L
in HEK293 cells expressing Na
V
1.5 with/without the β1 subunit or in NRCMs (Fig. 1A, B). SUMO1 enhanced membrane localization of Na
V
1.5 in HEK293 cells (Fig. 1C) with minimal changes to steady state activation, inactivation or channel kinetics.
Conclusion:
SUMOylation of Na
v
1.5 at K442 increases peak I
Na
without changing I
Na,L
, at least in part by altering membrane abundance. Our findings do not support SUMOylation as a mechanism for changes in I
Na,L
.
Details
- Title: Subtitle
- Abstract 14053: Sumoylation of the Cardiac Sodium Channel Na V 1.5 Does Not Increase Late Sodium Current
- Creators
- Jin-young Yoon - University of IowaAlexander Greiner - The Univ of Iowa, Iowa City, IAJulia Jacobs - Univ of Iowa, Iowa City, IAWilliam J Kutschke - University of IowaYoung-Rae Kim - University of IowaDaniel S Matasic - University of IowaHaider Mehdi - UNIVERSITY IOWA, Iowa City, IAKaikobad J Irani - University of IowaBarry London - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.144(Suppl_1)
- DOI
- 10.1161/circ.144.suppl_1.14053
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/16/2021
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Radiation Oncology
- Record Identifier
- 9984302998002771
Metrics
5 Record Views