What question did this study set out to answer?

To determine whether CaMKII activation mediates early and delayed afterdepolarizations triggered by hydrogen peroxide-induced oxidative stress in cardiac ventricular myocytes.

November 27, 2008Circulation ResearchOpen Access

Oxidative Stress–Induced Afterdepolarizations and Calmodulin Kinase II Signaling

View Full Paper

Ask AI

Bookmark

Why the study?

Does CaMKII inhibition prevent oxidative stress-induced afterdepolarizations in rabbit ventricular myocytes?

Key Points

To determine whether CaMKII activation mediates early and delayed afterdepolarizations triggered by hydrogen peroxide-induced oxidative stress in cardiac ventricular myocytes.
Conducted patch-clamp electrophysiology and intracellular calcium imaging in isolated rabbit ventricular myocytes loaded with Fluo-4 AM.
Exposed myocytes to hydrogen peroxide (0.2 to 1 mmol/L for 5 to 15 minutes) with and without ion channel blockers (tetrodotoxin, nifedipine) and CaMKII inhibitors (KN-93, KN-92, AIP peptide).
Hydrogen peroxide exposure consistently induced early afterdepolarizations (EADs) by enhancing peak and late L-type calcium current (I_Ca,L) and impairing sodium current (I_Na) inactivation, followed by delayed afterdepolarizations (DADs) via spontaneous sarcoplasmic reticulum calcium release.
CaMKII inhibition with KN-93 (1 µmol/L; n=4) completely prevented hydrogen peroxide-induced EADs and DADs compared to the inactive analog KN-92 (1 µmol/L; n=5), and the selective peptide inhibitor AIP (2 µmol/L) significantly delayed afterdepolarization onset.

Structured PICO

Does CaMKII inhibition prevent oxidative stress-induced afterdepolarizations in rabbit ventricular myocytes?

Population

Fluo-4 AM-loaded rabbit ventricular myocytes

Intervention

Exposure to H(2)O(2) (0.2 to 1 mmol/L) for 5 to 15 minutes, with CaMKII inhibitors (KN-93 1 micromol/L or AIP 2 micromol/L) or ion channel blockers (tetrodotoxin 10 micromol/L, nifedipine)

Comparator

Inactive analog KN-92 (1 micromol/L) or baseline conditions

Outcome

Occurrence of early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs)surrogate

Oxidative stress-induced afterdepolarizations depend on CaMKII activation, providing a mechanistic link to lethal ventricular arrhythmias in diseased hearts.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

CaMKII inhibition may mitigate oxidative arrhythmias; hypothesis-generating in myocytes and leaves open in vivo or clinical translation.

Cite This Study

Xie et al. (2008) studied this question.

synapsesocial.com/papers/6a1ef6f01baba023eb6b57c2 https://doi.org/10.1161/circresaha.108.183475

View Full Paper

Ask AI

Bookmark

Oxidative Stress–Induced Afterdepolarizations and Calmodulin Kinase II Signaling

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Oxidative Stress–Induced Afterdepolarizations and Calmodulin Kinase II Signaling

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider