Synapse
⌘+K
Synapse
PulseExploreJournal ClubResearchersJournals
Instagram
HomeJournal ClubExplore
January 21, 2011Circulation ResearchOpen Access

Reactive Oxygen Species–Activated Ca/Calmodulin Kinase IIδ Is Required for Late I Na Augmentation Leading to Cellular Na and Ca Overload

View Full Paper
Ask AI
Bookmark
Share

Population

Permeabilized rabbit cardiomyocytes, wild-type (WT) mouse myocytes, and CaMKIIδ(-/-) mouse myocytes

Comparison

H2O2 exposure; CaMKIIδ overexpression via… vs CaMKIIδ vs WT myocytes; CaMKII inhibition vs no…

Design

Preclinical

Key result

ROS-activated CaMKIIδ enhances late INa, leading to cellular Na and Ca overload, a process requiring free intracellular Ca and a functional sarcoplasmic reticulum.

Authors

SWStefan WagnerHRHanna Maria RuffSWSarah L. Weber

Discussion

Loading...

Member takes

Overview

Hypothesis-generating for CaMKIIδ inhibition in HF arrhythmias; extends mechanistic ROS-late INa insights in animal models.

Structured PICO

P
Population
Permeabilized rabbit cardiomyocytes, wild-type (WT) mouse myocytes, and CaMKIIδ(-/-) mouse myocytes
I
Intervention
H2O2 (40 μmol/L) exposure; CaMKIIδ overexpression via adenoviral gene transfer
C
Comparator
CaMKIIδ(-/-) vs WT myocytes; CaMKII inhibition (KN93 or AIP) vs no inhibition; absence of free Ca or SR depletion vs intact Ca/SR
O
Outcome
CaMKII oxidation and autophosphorylation, late INa, [Na]i and [Ca]i accumulation, and SR Ca spark frequencysurrogate

ROS-activated CaMKIIδ enhances late INa, leading to cellular Na and Ca overload, which requires free intracellular Ca and a functional SR and may contribute to arrhythmias in heart failure.

Cite This Study

Wagner et al. (2011) studied Heart failure (cellular Na and Ca overload). H2O2 (Reactive Oxygen Species) and CaMKIIδ modulation vs. Wild-type or CaMKII inhibition was evaluated on CaMKII oxidation, autophosphorylation, and late INa augmentation. ROS-activated CaMKIIδ enhances late INa, leading to cellular Na and Ca overload, a process requiring free intracellular Ca and a functional sarcoplasmic reticulum.

synapsesocial.com/papers/6a1ef6f01baba023eb6b57bfhttps://doi.org/10.1161/circresaha.110.221911
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Intracellular Na+ overload causes oxidation of CaMKII and leads to Ca2+ mishandling in isolated ventricular myocytes2014 · 57 citations
  2. 2Myocardial death and dysfunction after ischemia-reperfusion injury require CaMKIIδ oxidation2019 · 31 citations
  3. 3CaMKII and reactive oxygen species contribute to early reperfusion arrhythmias, but oxidation of CaMKIIδ at methionines 281/282 is not a determining factor2022 · 10 citations
  4. 4Redox Regulation of Sodium and Calcium Handling2012 · 156 citations
  5. 5A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na + loading and CaMKII2014 · 100 citations