Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

840
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...
840
Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacological Actions01:27

Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacological Actions

637
Nondepolarizing neuromuscular blockers prevent the membrane depolarization of muscle cells and inhibit muscle contraction. These are usually administered with anesthetics to achieve complete muscle relaxation. Upon administration, these drugs first block the small, rapidly contracting muscles of the face and hands, followed by the larger muscles of the trunk and the intercostal muscles. The diaphragm is the last muscle to be affected.
Although all competitive neuromuscular blockers are designed...
637
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

1.4K
Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
1.4K
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action01:17

Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action

2.3K
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
2.3K
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

1.2K
Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
1.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Biomolecular condensation of cMLCK enables myosin motor phosphorylation in the heart.

bioRxiv : the preprint server for biology·2026
Same author

Spatial control of myosin regulatory light chain phosphorylation modulates cardiac thick filament mechanosensing.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Development of bifunctional fluorescent probes and their application to α-helix labelling.

Organic & biomolecular chemistry·2025
Same author

Structural changes in troponin during activation of skeletal and heart muscle determined in situ by polarised fluorescence.

Biophysical reviews·2025
Same author

Cardiac myosin binding protein-C phosphorylation as a function of multiple protein kinase and phosphatase activities.

Nature communications·2024
Same author

Synthesis and Biophysical Characterization of Fingolimod Derivatives as Cardiac Troponin Antagonists.

ACS medicinal chemistry letters·2024

Related Experiment Video

Updated: Oct 20, 2025

Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
08:39

Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Published on: December 22, 2020

4.3K

A Potent Fluorescent Reversible-Covalent Inhibitor of Cardiac Muscle Contraction.

Fangze Cai1, Thomas Kampourakis2, Brittney A Klein1

  • 1Department of Biochemistry, University of Alberta, Edmonton AB T6G 2R3, Canada.

ACS Medicinal Chemistry Letters
|September 17, 2021
PubMed
Summary

Researchers discovered DN-F01, a novel cardiac sarcomere inhibitor targeting the troponin complex. This compound shows potent, calcium-dependent inhibition of cardiac myofibrillar ATPase activity, offering potential for treating cardiac diseases.

More Related Videos

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
09:36

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

Published on: December 22, 2023

1.4K
Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes
07:32

Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes

Published on: May 25, 2022

1.6K

Related Experiment Videos

Last Updated: Oct 20, 2025

Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
08:39

Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Published on: December 22, 2020

4.3K
Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
09:36

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

Published on: December 22, 2023

1.4K
Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes
07:32

Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes

Published on: May 25, 2022

1.6K

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Drug Discovery

Background:

  • Modulating cardiac sarcomere function is a therapeutic strategy for heart disease.
  • Sarcomere activators are well-studied, but inhibitors are scarce.
  • Identifying novel sarcomere inhibitors is crucial for developing new cardiac treatments.

Purpose of the Study:

  • To identify and characterize novel inhibitors of the cardiac sarcomere.
  • To investigate the mechanism of action of a newly discovered inhibitor, DN-F01.
  • To explore the potential of DN-F01 in modulating cardiac muscle contractility.

Main Methods:

  • Biochemical assays measuring cardiac myofibrillar ATPase activity.
  • Fluorescence spectroscopy to determine binding affinity to troponin complex.
  • Nuclear Magnetic Resonance (NMR) titration to elucidate binding modes.

Main Results:

  • DN-F01 demonstrated potent, calcium-dependent inhibition of cardiac myofibrillar ATPase activity (IC50 = 11 ± 4 nmol/L).
  • Fluorescence spectroscopy revealed binding of DN-F01 to a cardiac troponin C-troponin I chimera (cChimera) with a KD of ~50 nM.
  • NMR studies indicated both covalent and noncovalent binding of DN-F01 to the calcium-saturated cChimera.

Conclusions:

  • DN-F01 is a potent inhibitor of the cardiac sarcomere, likely targeting the troponin complex.
  • The compound exhibits significant calcium-dependent inhibitory effects on cardiac myofibrillar ATPase.
  • DN-F01 represents a promising lead compound for developing novel therapeutics for cardiac diseases.