Related Experiment Video
Updated: May 20, 2026
10:05
Measurement of Calcium Fluctuations Within the Sarcoplasmic Reticulum of Cultured Smooth Muscle Cells Using FRET-based Confocal Imaging
Published on: June 20, 2016
Switch from ER-mitochondrial to SR-mitochondrial calcium coupling during muscle differentiation
Muqing Yi1, David Weaver, Verónica Eisner
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cell Calcium
|July 13, 2012
Summary
Mitochondria couple to calcium release sites in muscle cells. Ryanodine receptor (RyR) expression during muscle differentiation enables this coupling, but doesn't alter mitochondrial shape.
Area of Science:
- Cell Biology
- Muscle Physiology
- Mitochondrial Dynamics
Background:
- Mitochondria dynamically regulate cellular calcium ([Ca2+]) by coupling to endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) Ca2+ release channels.
- The developmental transition in mitochondrial coupling from ER in myoblasts to SR in differentiated muscle fibers is not well understood.
- Understanding this transition is crucial for comprehending how cellular metabolism matches activity levels.
Purpose of the Study:
- To investigate the mechanism of developmental transition in mitochondrial coupling to Ca2+ release channels.
- To analyze mitochondrial sensing of inositol trisphosphate receptor (IP3R) and ryanodine receptor (RyR)-mediated Ca2+ signals.
- To examine changes in mitochondrial morphology during muscle differentiation.
Main Methods:
- Studied mitochondrial Ca2+ ([Ca2+]m) and cytoplasmic Ca2+ ([Ca2+]c) dynamics in H9c2 myoblasts and differentiating myotubes.
- Utilized specific agonists (vasopressin for IP3R, caffeine for RyR) to trigger Ca2+ release.
- Employed exogenous expression of RyR1 in myoblasts to assess its role in coupling.
Main Results:
- Myoblasts exhibit elongated mitochondria and respond primarily to IP3R-mediated Ca2+ signals, while differentiating myotubes show globular mitochondria and respond to RyR-mediated Ca2+ signals.
- Both IP3R and RyR activation were closely associated with mitochondrial Ca2+ uptake, indicating local ER/SR-mitochondrial coupling.
- Exogenous RyR1 expression in myoblasts induced mitochondrial Ca2+ signaling but did not alter mitochondrial morphology, suggesting RyR expression is sufficient for coupling but not for morphological changes.
Conclusions:
- Muscle differentiation involves a shift in mitochondrial coupling from IP3Rs to RyRs, coinciding with RyR expression.
- RyR expression is sufficient to establish functional coupling between Ca2+ release sites and mitochondria.
- Mitochondrial proliferation and reshaping during differentiation occur through pathways independent of RyR expression.
Related Concept Videos
01:26Cross-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.
01:27Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:25Smooth Muscle Contraction
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
01:29Relaxation 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.
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.
01:20Excitation-Contraction Coupling in Skeletal Muscles
Excitation-contraction coupling is a series of events that occur between generating an action potential and initiating a muscle contraction. It occurs at the triad, a structure found in skeletal muscle fibers that comprise a T-tubule and terminal cisternae of the sarcoplasmic reticulum on each side. These triads are visible in longitudinally sectioned muscle fibers. They are typically located at the A-I junction — the junction between the A and I bands of the sarcomere.
When an action potential...
When an action potential...
01:13Formation of Muscle Fibers from Myoblasts
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...