Related Experiment Video

Updated: Nov 17, 2025

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
11:00

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Published on: September 18, 2017

10.4K

Stress-driven cardiac calcium mishandling via a kinase-to-kinase crosstalk

Charia McKee1, Dan J Bare1, Xun Ai2

  • 1Department of Physiology & Biophysics, Rush University Medical Center, 1750 West Harrison St. 1255 Jelke, Chicago, IL, 60612-3825, USA.

Pflugers Archiv : European Journal of Physiology
|February 16, 2021
PubMed

Insights

The stress kinase JNK2 plays a dual role in regulating CaMKIIδ, impacting calcium handling in cardiomyocytes. This finding is crucial for understanding cardiac remodeling under stress.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cellular Physiology

Background:

  • Cardiomyocyte calcium homeostasis is vital for cardiac function.
  • Abnormal calcium dynamics, including SR Ca2+-ATPase uptake and SR calcium leak, contribute to pathological cardiac remodeling.
  • Ca2+/calmodulin-dependent protein kinase II-δ (CaMKIIδ) is a key mediator of calcium dysregulation in cardiomyocytes.

Purpose of the Study:

  • To review cardiac SR calcium handling in physiological and pathological states.
  • To highlight the newly identified role of stress-activated c-jun N-terminal kinase (JNK) isoform 2 (JNK2) in CaMKIIδ-dependent SR calcium mishandling.
  • To discuss the dual functions of JNK2 in CaMKIIδ expression and activation within stressed cardiomyocytes.

Main Methods:

  • Literature review focusing on cardiac calcium handling and stress kinase pathways.
  • Analysis of recent findings on JNK2's interaction with CaMKIIδ.
  • Discussion of molecular mechanisms underlying SR calcium mishandling.

Main Results:

  • JNK2 directly influences both the expression and activation of CaMKIIδ.
  • JNK2 contributes to CaMKIIδ-dependent SR calcium mishandling in stressed hearts.
  • Elevated cellular stress activates JNK, a key kinase in pathological remodeling.

Conclusions:

  • JNK2 emerges as a critical regulator of CaMKIIδ, influencing cardiac calcium handling.
  • Understanding JNK2's dual role provides new insights into stress-induced cardiac remodeling.
  • Targeting the JNK2-CaMKIIδ pathway may offer therapeutic strategies for heart conditions.

Keywords:
Ca2+/calmodulin-dependent protein kinase IICalcium handlingDiastolic calcium leakSarcoplasmic reticulumc-jun N-terminal kinase

More Related Videos

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling08:29

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling

Published on: August 1, 2016

9.7K
Cytosolic Calcium Measurements in Renal Epithelial Cells by Flow Cytometry10:24

Cytosolic Calcium Measurements in Renal Epithelial Cells by Flow Cytometry

Published on: October 28, 2014

15.5K

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.6K
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.7K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
15.2K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.1K
Cross-bridge Cycle01:26

Cross-bridge Cycle

As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
120.7K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.3K