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

G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Mechanism of Cardiac Arrhythmias01:28

Mechanism of Cardiac Arrhythmias

Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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...
Electrophysiology of Normal Cardiac Rhythm01:19

Electrophysiology of Normal Cardiac Rhythm

The normal cardiac rhythm is a synchronized electrical activity that facilitates the regular and coordinated contraction of the heart muscle. This process is essential for efficient blood circulation throughout the body. The fundamental elements involved in establishing and maintaining this rhythm include the unique electrical properties of cardiac muscle cells, the sinoatrial (SA) node's pacemaker function, the specialized conducting system, and the ionic mechanisms underlying each phase of...
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium...

You might also read

Related Articles

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

Sort by
Same author

Targeting Late Na<sup>+</sup> Current: Too Late or Better Late Than Never?

Circulation research·2026
Same author

Heterozygous Loss of Scn1b Results in Concealed Conduction Phenotype Unmasked by Osmotic Stress.

bioRxiv : the preprint server for biology·2026
Same author

Side-viewing probe for lesion depth mapping on the left ventricle epicardium with near-infrared spectroscopy.

Scientific reports·2026
Same author

Patient and arrest characteristics associated with rearrest and mortality following out of hospital cardiac arrest.

Resuscitation plus·2026
Same author

Multimodal PSOCT-NIRS catheter for guided ablation of atrial fibrillation.

Journal of biomedical optics·2026
Same author

Intercalated disk structure, tissue heterogeneity and ion channel distribution modulate conduction and local calcium influx.

The Journal of physiology·2026

Related Experiment Video

Updated: Jul 18, 2026

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

Ryanodine receptor dysfunction and triggered activity in the heart.

Rodolphe P Katra1, Toshiyuki Oya, Gregory S Hoeker

  • 1MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH 44109-1998, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|December 26, 2006
PubMed
Summary

Cardiac ryanodine receptor (RyR) dysfunction causes triggered activity and arrhythmias through spontaneous calcium release (SCR) events. These SCR events are linked to faster epicardial calcium reuptake, not just cytoplasmic levels.

More Related Videos

Functional Characterization of Endogenously Expressed Human RYR1 Variants
07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella
11:31

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella

Published on: November 30, 2018

Related Experiment Videos

Last Updated: Jul 18, 2026

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

Functional Characterization of Endogenously Expressed Human RYR1 Variants
07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella
11:31

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella

Published on: November 30, 2018

Area of Science:

  • Cardiovascular Physiology
  • Cardiac Electrophysiology
  • Molecular Cardiology

Background:

  • Arrhythmogenesis is increasingly linked to cardiac ryanodine receptor (RyR) dysfunction.
  • The precise mechanisms connecting abnormal RyR function to heart arrhythmias remain unclear.
  • Transmural heterogeneities in calcium handling are hypothesized to play a role in RyR-mediated triggered activity.

Purpose of the Study:

  • To investigate the mechanistic link between abnormal cardiac ryanodine receptor (RyR) function and triggered activity leading to arrhythmogenesis.
  • To determine if spontaneous calcium release (SCR) events, dependent on transmural calcium handling heterogeneities, cause triggered activity under abnormal RyR conditions.
  • To explore the role of calcium reuptake kinetics in the generation of arrhythmias associated with RyR dysfunction.

Main Methods:

  • Utilized high-resolution optical mapping of intracellular calcium and transmembrane potential in canine left ventricular wedge preparations (n=28).
  • Induced abnormal RyR conditions using FKBP12.6 dissociation via rapamycin and beta-adrenergic stimulation with isoproterenol.
  • Initiated triggered activity through rapid pacing under both normal and abnormal RyR conditions.

Main Results:

  • Abnormal RyR conditions, unlike control or single interventions, consistently led to spontaneous calcium release (SCR) events and triggered activity in nearly all preparations.
  • Complex arrhythmias, including monomorphic and polymorphic tachycardia, were frequently observed under abnormal RyR conditions.
  • Triggered activity and SCRs occurred preferentially near the epicardium, correlating with faster calcium reuptake kinetics rather than elevated cytoplasmic calcium levels.
  • Arrhythmias resolved upon washout of the interventions, confirming the role of induced RyR dysfunction.

Conclusions:

  • Abnormal cardiac ryanodine receptor (RyR) function induces triggered activity and arrhythmias via spontaneous calcium release (SCR) events.
  • Faster calcium reuptake kinetics near the epicardium, rather than cytoplasmic calcium levels, are critical for SCR-dependent triggered activity.
  • Multiple regions of SCR may underlie the multifocal arrhythmias observed in conditions of RyR dysfunction.