10.15140/DV92-P553
Hegyi, Bence
0000-0003-3113-221X
UC Davis
Chen-Izu, Ye
0000-0003-4818-9570
UC Davis
Data deposition for Complex electrophysiological remodeling in
postinfarction ischemic heart failure
UC Davis
2018
Heart failure
Myocardial Infarction
Electrophysiology
Action potentials
Ionic current
National Heart, Lung, and Blood Institute
R01-HL123526
National Heart, Lung, and Blood Institute
R01-HL90880
National Heart, Lung, and Blood Institute
P01-HL080101
National Heart, Lung, and Blood Institute
R01-HL30077
National Heart, Lung, and Blood Institute
R01-HL085727
National Heart, Lung, and Blood Institute
R01-HL085844
U.S. Department of Veterans Affairs
I01 BX000576
U.S. Department of Veterans Affairs
I01 CX001490
Országos Tudományos Kutatási Alapprogramok
OTKA101196
California Institute of Regenerative Medicine
TR3 05626
American Heart Association
14GRNT20510041
2018-03-03T01:12:26Z
en
dataset
10.1073/pnas.1718211115
4805994920 bytes
1
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Heart failure (HF) following myocardial infarction (MI) is associated with
high incidence of cardiac arrhythmias. Development of therapeutic strategy
requires detailed understanding of electrophysiological remodeling.
However, changes of ionic currents in ischemic HF remain incompletely
understood, especially in translational large animal models. Here, we
systematically measure the major ionic currents in ventricular myocytes
from the infarct border and remote zones in a porcine model of post-MI HF.
We recorded eight ionic currents during the cell’s action potential (AP)
under physiologically relevant conditions using selfAP-clamp Sequential
Dissection. Compared to healthy controls, HF-remote zone myocytes
exhibited increased late Na+ current, Ca2+-activated K+ current,
Ca2+-activated Cl- current, decreased rapid delayed rectifier K+ current,
and altered Na+/Ca2+ exchange current profile. In HF-border zone myocytes,
the above changes also occurred but with additional decrease of L-type
Ca2+ current, decrease of inward rectifier K+ current, and Ca2+
release-dependent delayed afterdepolarizations. Our data reveal that the
changes in any individual current are relatively small, but the integrated
impacts shift the balance between the inward and outward currents to
shorten AP in the border zone but prolong AP in the remote zone. This
differential remodeling in post-MI HF increases the inhomogeneity of AP
repolarization which may enhance the arrhythmogenic substrate. Our
comprehensive findings provide a new mechanistic framework for
understanding why single channel blockers may fail to suppress
arrhythmias, and highlight the need to consider the rich tableau and
integration of many ionic currents in designing therapeutic strategies for
treating arrhythmias in HF.
Electrophysiology data were collected using pClamp10 (Molecular Devices)
software, then Clampfit 10 (Molecular Devices), Excel 2016 (Microsoft) and
Origin 2016 (OriginLab) softwares were used for data processing and
analysis. Calcium and contraction data were collected using IonWizard
(IonOptix) software, then IonWizard, Excel and Origin softwares were used
for data processing and analysis. Files are compressed to keep the folder
structure and to ease the navigation between the uploaded documents.
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