Related Experiment Video

Updated: May 21, 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

Carbonylation induces heterogeneity in cardiac ryanodine receptor function in diabetes mellitus

Chun Hong Shao1, Chengju Tian, Shouqiang Ouyang

  • 1Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5800, USA.

Molecular Pharmacology
|June 1, 2012
PubMed

Insights

Diabetes increases heart failure risk by altering cardiac ryanodine receptors (RyR2s). Reactive carbonyl species (RCS) modify RyR2s, causing abnormal calcium release and contributing to heart dysfunction in diabetes.

Area of Science:

  • Cardiovascular Biology
  • Diabetology
  • Molecular Cardiology

Background:

  • Diabetes mellitus significantly elevates risks for heart failure and arrhythmias.
  • Cardiac type 2 ryanodine receptors (RyR2s), crucial for sarcoplasmic reticulum calcium release, are implicated in these diabetic cardiac complications.
  • Mechanisms behind RyR2 dysfunction in diabetes are not fully understood.

Purpose of the Study:

  • To investigate the role of post-translational modification by reactive carbonyl species (RCS) in RyR2 dysregulation in a rat model of type 1 diabetes.
  • To elucidate the impact of RCS modification on RyR2 function and calcium handling in the diabetic heart.

Main Methods:

  • Utilized a type 1 diabetes rat model, echocardiography, hemodynamic studies, confocal microscopy, Western blotting, mass spectrometry, site-directed mutagenesis, and radioligand binding assays.
  • Assessed spontaneous and evoked calcium release in ventricular myocytes.
  • Analyzed RyR2 protein levels, RCS adducts, and [(3)H]ryanodine binding.

Main Results:

  • Diabetic rats exhibited a ~5-fold increase in spontaneous Ca(2+) release and dyssynchronous evoked Ca(2+) release.
  • RyR2 protein levels were unchanged, but [(3)H]ryanodine binding was reduced, indicating functional alterations.
  • Mass spectrometry identified RCS adducts on RyR2, and mutations confirmed the impact of carbonylation on channel function.
  • Methylglyoxal exposure mimicked and exacerbated RyR2 dysfunction, including spontaneous Ca(2+) release and Ca(2+) waves.
  • RCS scavenger treatment in diabetic rats normalized Ca(2+) release, reduced RyR2 carbonylation, and restored [(3)H]ryanodine binding.

Conclusions:

  • Post-translational modification of RyR2 by reactive carbonyl species (RCS) is a significant contributor to RyR2 dysfunction in experimental diabetes.
  • RCS-mediated modifications lead to aberrant calcium handling, promoting cardiac arrhythmias and heart failure in diabetic conditions.
  • Targeting RCS modification of RyR2 may offer a therapeutic strategy for diabetic cardiomyopathy.

More Related Videos

Functional Characterization of Endogenously Expressed Human RYR1 Variants07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

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

Type I Diabetes II: Pathophysiology01:26

Type I Diabetes II: Pathophysiology

Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular uptake of...
Type II Diabetes II: Pathophysiology01:24

Type II Diabetes II: Pathophysiology

PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
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.
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...
Type II Diabetes I: Introduction01:26

Type II Diabetes I: Introduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, in which target tissues such as the liver, muscle, and adipose tissue respond poorly to insulin. It is also associated with inadequate compensatory insulin secretion, where pancreatic β-cells fail to produce sufficient insulin. Together, these abnormalities lead to persistent hyperglycemia.EtiologyT2DM develops through a complex interaction of genetic predisposition and environmental or...
Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...