Related Experiment Video

Updated: Oct 1, 2026

Functional Characterization of Endogenously Expressed Human RYR1 Variants
07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

Altered communication between L-type calcium channels and ryanodine receptors in heart failure

Jean-Pierre Bénitah1, Benoît Gilles Kerfant, Guy Vassort

  • 1INSERM U-390, Montpellier, France.

Frontiers in Bioscience : a Journal and Virtual Library
|May 7, 2002
PubMed

Insights

Heart failure (HF) impairs cardiomyocyte contraction by disrupting excitation-contraction coupling. Reduced efficiency of calcium (Ca2+) release from the sarcoplasmic reticulum, linked to T-tubule reorganization, underlies this depressed function in failing hearts.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cell Physiology

Background:

  • Heart failure (HF) is a progressive syndrome characterized by decreased cardiac contractile function.
  • Cardiomyocyte contraction relies on excitation-contraction (EC) coupling, involving calcium (Ca2+) influx through DHPRs and subsequent Ca2+ release from the sarcoplasmic reticulum (SR) via RyRs.
  • Understanding the mechanisms of depressed cardiac function in HF is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the underlying mechanisms of impaired EC coupling in failing cardiomyocytes.
  • To analyze the efficiency of Ca2+ handling and release in the context of HF.
  • To elucidate the role of structural changes in T-tubules and SR in HF-related contractile dysfunction.

Main Methods:

  • Analysis of excitation-contraction coupling elements in cardiomyocytes from failing and non-failing hearts.
  • Measurement of calcium (Ca2+) current density (ICa) and sarcoplasmic reticulum (SR) Ca2+ release.
  • Assessment of DHPR-RyR coupling efficiency and Ca2+ spark frequency.
  • Evaluation of T-tubule density in failing myocytes.

Main Results:

  • While Ca2+ current (ICa) density is generally maintained in HF, SR Ca2+ release is significantly reduced.
  • The efficacy of ICa in triggering SR Ca2+ release is diminished in failing myocytes.
  • In terminal HF without hypertrophy, reduced SR Ca2+ load contributes to decreased SR Ca2+ release.
  • In hypertrophied failing myocytes, fewer Ca2+ sparks are triggered by equivalent ICa, suggesting altered T-tubule/junctional SR organization.
  • Reduced T-tubule density in failing cells supports theories of functional or spatial reorganization.

Conclusions:

  • Impaired excitation-contraction coupling in heart failure is multifactorial, involving reduced SR Ca2+ release and diminished DHPR-RyR coupling efficiency.
  • Structural alterations, particularly reduced T-tubule density, contribute to altered Ca2+ handling and contractile dysfunction in HF.
  • Further research into these mechanisms can guide therapeutic strategies for heart failure.

More Related Videos

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes11:00

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

Published on: September 18, 2017

Imaging Ca2+ Signals in Small Pulmonary Veins at Physiological Intraluminal Pressures05:35

Imaging Ca2+ Signals in Small Pulmonary Veins at Physiological Intraluminal Pressures

Published on: March 21, 2025

Related Concept Videos

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,...
Antianginal Drugs: Calcium Channel Blockers and Ranolazine01:25

Antianginal Drugs: Calcium Channel Blockers and Ranolazine

Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
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...
Heart Failure Drugs: Diuretics01:22

Heart Failure Drugs: Diuretics

Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...