What is the clinical evidence from this study?

Study design: Other. Population: Cardiac arrhythmias and oxidative stress. Intervention: H2O2 (oxidative stress) vs. Vehicle. Primary outcome: Action potential duration at 90% repolarization (APD90) in WT cardiomyocytes at 2 minutes (p=0.0006).

What does this research mean for the field?

Exposure to oxidative stress prolongs action potential duration and increases early afterdepolarizations in murine cardiomyocytes through the inhibition of potassium currents by oxidation-activated protein kinase A type I. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

October 9, 2020Open Access

Inhibition of cardiac potassium currents by oxidation-activated protein kinase A contributes to early afterdepolarizations in the heart

MTMaximilian TrumUniversity Hospital Regensburg MIMd. Monirul IslamUniversity of Dhaka SLSimon LebekElectrophysiology

Key Result

Exposure to H2O2 significantly prolonged action potential duration and increased early afterdepolarizations in wild-type murine cardiomyocytes, an effect absent in redox-dead PKA knock-in mice.

Structured PICO

Population

murine ventricular cardiomyocytes

Intervention

Oxidation-activated PKA type I

Outcome

inhibition of transient outward potassium current (I to) and inward rectifying potassium current (I K1), APD prolongation, and generation of early afterdepolarizationssurrogate

Oxidation-activated PKA type I plays a mechanistic role in ROS-induced action potential prolongation and early afterdepolarizations in murine cardiomyocytes.

Main Result

Absolute Event Rate: 107.6% vs 53.42%

p-value: p=0.0006

Limitations

H2O2 exposure does not result in a selective oxidation of PKA, as there are many other targets for ROS-dependent oxidation.
The use of BaCl2 to inhibit IK1 is voltage-dependent, which could lead to an underestimation of IK1 at more positive membrane potentials.
Species differences in the contribution of Ito to membrane repolarization between murine and human ventricular myocytes.

Abstract

Oxidation-activated PKA type I inhibits transient outward potassium current ( I to ) and inward rectifying potassium current ( I K1 ) and contributes to ROS-induced APD prolongation as well as generation of early afterdepolarizations in murine ventricular cardiomyocytes.

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Cite This Study

Trum et al. (Fri,) conducted a other in Cardiac arrhythmias and oxidative stress. H2O2 (oxidative stress) vs. Vehicle was evaluated on Action potential duration at 90% repolarization (APD90) in WT cardiomyocytes at 2 minutes (p=0.0006). Exposure to H2O2 significantly prolonged action potential duration and increased early afterdepolarizations in wild-type murine cardiomyocytes, an effect absent in redox-dead PKA knock-in mice.

synapsesocial.com/papers/6a16d97d2fcf950e00055ca6 https://doi.org/https://doi.org/10.1152/ajpheart.00182.2020

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