Related Experiment Video

Updated: May 19, 2026

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

Enhanced binding of calmodulin to the ryanodine receptor corrects contractile dysfunction in failing hearts

Akihiro Hino1, Masafumi Yano, Takayoshi Kato

  • 1Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.

Cardiovascular Research
|August 16, 2012
PubMed
Abstract

Insights

Reduced calmodulin (CaM) binding to the cardiac ryanodine receptor (RyR2) contributes to heart failure by causing abnormal calcium release. Restoring CaM binding to RyR2 normalizes channel function and improves heart contractility.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Calcium Signaling

Background:

  • Cardiac ryanodine receptor (RyR2) function is modulated by calmodulin (CaM).
  • The role of CaM in abnormal calcium release during heart failure is not fully understood.

Purpose of the Study:

  • To investigate the pathogenic role of defective CaM binding to RyR2 in heart failure-associated channel dysfunction.
  • To explore the therapeutic potential of enhancing CaM binding to RyR2.

Main Methods:

  • Assessed CaM involvement in aberrant calcium release in normal and failing canine hearts.
  • Utilized the CaM isoform Gly-Ser-His-CaM (GSH-CaM) to restore CaM binding to RyR2.
  • Measured calcium spark frequency (SpF) and sarcoplasmic reticulum (SR) Ca(2+) content in myocytes.

Main Results:

  • CaM binding affinity to RyR2 was significantly lower in failing hearts.
  • Failing myocytes exhibited increased SpF and reduced SR Ca(2+) content.
  • GSH-CaM expression corrected aberrant SpF and SR Ca(2+) content in failing myocytes.

Conclusions:

  • Reduced CaM binding to RyR2 is critical in the pathogenesis of aberrant calcium release in heart failure.
  • Restoring CaM binding to RyR2 stabilizes channel function, normalizing calcium handling and contractile function.

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

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia09:36

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia

Published on: December 22, 2023

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,...
Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
Smooth Muscle Contraction01:25

Smooth Muscle Contraction

Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...