Related Experiment Video

Updated: Dec 9, 2025

Functional Characterization of Endogenously Expressed Human RYR1 Variants
07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

2.9K

Structure and Function of the Human Ryanodine Receptors and Their Association with Myopathies-Present State,

Vladena Bauerová-Hlinková1, Dominika Hajdúchová1, Jacob A Bauer1

  • 1Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská Cesta 21, 845 51 Bratislava, Slovakia.

Molecules (Basel, Switzerland)
|September 9, 2020
PubMed

Insights

Mutations in ryanodine receptor genes (RYR1 and RYR2) cause defective calcium (Ca2+) release, leading to life-threatening cardiac arrhythmias and muscle syndromes. This review details disease-causing mutations and structural changes in these critical ion channels.

Area of Science:

  • Cardiovascular Biology
  • Molecular Physiology
  • Biophysics

Background:

  • Cardiac arrhythmias are life-threatening conditions often caused by calcium (Ca2+) influx dysregulation in cardiomyocytes.
  • Ryanodine receptors (RyR1 and RyR2) are key Ca2+ release channels; their dysfunction, particularly RyR2, is linked to heart rhythm disorders.
  • Mutations in RYR1 and RYR2 genes can lead to various syndromes, including less severe but still dangerous conditions.

Purpose of the Study:

  • To provide an overview of frequent diseases caused by RyR1 and RyR2 mutations.
  • To review recent experimental structural studies of RyR1 and RyR2.
  • To summarize computational dynamics work and known structural/functional changes in RyR1/RyR2, focusing on specific domains.

Main Methods:

  • Literature review of diseases associated with RYR1 and RYR2 mutations.
  • Summary of recent experimental structural biology findings for RyR1 and RyR2.
  • Review of computational studies on RyR1 and RyR2 dynamics and function.

Main Results:

  • Identified three main mutation 'hot spots' in RYR1 and RYR2 genes.
  • Mutations alter channel structure, interdomain properties, binding interactions, and dynamics.
  • Defective Ca2+ release from the sarcoplasmic reticulum is a common outcome, impacting myocyte function.

Conclusions:

  • RyR1 and RyR2 mutations significantly impact Ca2+ handling and cellular function.
  • Understanding structural and dynamic changes is crucial for elucidating disease mechanisms.
  • Further research into RyR structure-function relationships can inform therapeutic strategies for arrhythmias and related syndromes.
Keywords:
cardiac arrhythmiascryo-electron microscopycrystal structuremolecular dynamicsmutationmyopathynormal mode analysisryanodine receptor

More Related Videos

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella11:31

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

Published on: November 30, 2018

7.7K
Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein Oligomerization: The Ryanodine Receptor Case Study12:43

Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein Oligomerization: The Ryanodine Receptor Case Study

Published on: July 27, 2016

11.9K

Related Concept Videos

Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin01:26

Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin

Directly acting muscle relaxants like dantrolene and botulinum toxin (BoNT) have distinct mechanisms and applications. Dantrolene, a hydantoin derivative, acts on the ryanodine receptor (RYR1) in skeletal muscle cells. RYR1 are calcium channels present at the sarcoplasmic reticulum membrane. In response to excitation, they release calcium ions from the sarcoplasmic reticulum to the cytosol. Calcium promotes actin-myosin-mediated contraction of muscles.
The binding of dantrolene to the RYR1...
970
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...
307
Overview of Myosin Structure and Function01:15

Overview of Myosin Structure and Function

Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X)  have been well...
5.7K
Relaxation of Skeletal Muscles01:29

Relaxation of Skeletal Muscles

The period of muscle contraction primarily influences the duration of stimulation at the neuromuscular junction (NMJ), the presence of free calcium ions in the sarcoplasm, and the availability of energy or ATP to support contractions.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open....
5.2K
The Role of Actin and Myosin in Non-muscle Cells01:10

The Role of Actin and Myosin in Non-muscle Cells

Actin and myosin or actomyosin filaments also play a significant role in cells other than those involved in muscle contraction (which occurs within the sarcomere of muscle cells). The mechanism of non-muscle cell contractile bundles was first observed in Dictyostelium and Acanthamoeba. In non-muscle cells, two bundles are commonly found: stress fibers and actomyosin adherence belts. These contractile bundles are smaller and less organized than the ones found in muscle cells. They  are held...
4.2K
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.
121.3K