Redox modulation of diaphragm contractility: Interaction between DHPR and RyR channels
John M Lawler1, Jong-hee Kim, Hyo-Bum Kwak
1Department of Health and Kinesiology, Interdisciplinary Faculty of Nutrition, Texas A&M University, College Station, TX 77843-4243, USA. jml2621@neo.tamu.edu
Free Radical Biology & Medicine
|October 6, 2010
Summary
Reactive oxygen species (ROS) affect diaphragm muscle contractility. Dihydropyridine receptors (DHPR) and ryanodine receptors (RyR) interact to modulate muscle force, particularly in the diaphragm.
Area of Science:
- Muscle Physiology
- Cellular Biology
- Biochemistry
Background:
- Reactive oxygen species (ROS) are known to modulate skeletal muscle contractility.
- Dihydropyridine receptors (DHPR) and calcium handling in the sarcoplasmic reticulum (SR) are potential redox-sensitive targets.
- The diaphragm, reliant on external calcium, is a key muscle for studying these effects at body temperature.
Purpose of the Study:
- To investigate the role of DHPR and ryanodine receptors (RyR) in ROS-mediated contractility modulation in intact rat diaphragm muscle.
- To understand the interactive mechanisms between DHPR and RyR in response to oxidative stress.
Main Methods:
- Isolated rat diaphragm fiber bundles were subjected to contractility assays.
- Oxidative stress was induced using xanthine oxidase (XO).
- Specific antagonists (ruthenium red, nitrendipine) and agonists (caffeine) were used to probe receptor function.
Main Results:
- ROS challenge induced a biphasic, dose- and time-dependent effect on diaphragm contractility, with potentiation observed at low XO concentrations.
- ROS-induced potentiation was partially reversible with washout and antioxidants (dithiothreitol, EUK-134).
- DHPR and RyR antagonists/agonists modulated ROS effects, indicating their involvement and interaction.
Conclusions:
- DHPR and RyR function are interactively modulated by ROS in intact diaphragm muscle.
- These redox-sensitive mechanisms significantly impact diaphragm contractility.
- Findings highlight the complex interplay of calcium channels and ROS in muscle function.
More Related Videos
12:35Optogenetic Inhibition of Rho1-Mediated Actomyosin Contractility Coupled with Measurement of Epithelial Tension in Drosophila Embryos
Published on: April 14, 2023
12:43Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein Oligomerization: The Ryanodine Receptor Case Study
Published on: July 27, 2016
Related Concept Videos
01:22Physiology of Respiration II: Neurogenic Control of Respiration
The neurogenic control of respiration coordinates various neural networks and pathways to regulate breathing rate and depth, meeting the body's oxygen and carbon dioxide exchange requirements. This system adapts to physiological and environmental conditions, ensuring optimal breathing patterns.
Central Control
The brainstem is the primary site of central control, hosting respiratory centers:
Central Control
The brainstem is the primary site of central control, hosting respiratory centers:
01:18Respiratory Regulation of Acid-Base Balance
Respiratory compensation is a vital physiological process that stabilizes blood plasma pH by regulating the partial pressure of carbon dioxide (PCO2), a key determinant of pH levels. Most carbon dioxide in the blood dissolves and converts into carbonic acid (H2CO3). It dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3⁻). There is also an inverse relationship between PCO2 and pH.
When carbon dioxide levels increase in the blood, more H+ and HCO3⁻ are produced, leading to a...
When carbon dioxide levels increase in the blood, more H+ and HCO3⁻ are produced, leading to a...
01:23Physiological Control of Respiration
Introduction
Breathing, a seemingly passive process, is regulated by the respiratory center in the brainstem. This center coordinates the involuntary control of respirations, which means it occurs without conscious effort, ensuring a smooth and uninterrupted pattern.
Regulation of Ventilation
The body maintains ventilation by monitoring levels of carbon dioxide (CO2), oxygen (O2), and hydrogen ion concentration (pH) in the arterial blood. Among these factors, the level of CO2 plays a crucial...
Breathing, a seemingly passive process, is regulated by the respiratory center in the brainstem. This center coordinates the involuntary control of respirations, which means it occurs without conscious effort, ensuring a smooth and uninterrupted pattern.
Regulation of Ventilation
The body maintains ventilation by monitoring levels of carbon dioxide (CO2), oxygen (O2), and hydrogen ion concentration (pH) in the arterial blood. Among these factors, the level of CO2 plays a crucial...
01:21G-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,...
Sensory organs,...
01:31Chemical Factors Affecting Respiration Centers
Chemical factors such as changing CO2, O2, and H+ levels in arterial blood play a critical role in influencing respiration depth and rates. These variations are detected by chemoreceptors—specialized sensors located in two primary body areas. Central chemoreceptors are found throughout the brain stem, including the ventrolateral medulla, while peripheral chemoreceptors are located in the aortic arch and carotid arteries.
CO2 has a potent influence on respiration and is strictly regulated. Under...
CO2 has a potent influence on respiration and is strictly regulated. Under...
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.