Calcium movements inside the sarcoplasmic reticulum of cardiac myocytes

Donald M Bers1, Thomas R Shannon

  • 1Department of Pharmacology, University of California, Davis, Davis, CA, USA. dmbers@ucdavis.edu

Insights

Sarcoplasmic reticulum (SR) calcium content ([Ca]SRT) is vital for heart function. Understanding intra-SR free calcium ([Ca]SR) dynamics is key to treating cardiac dysfunction and arrhythmias.

Area of Science:

  • Cardiology
  • Cell Physiology
  • Biophysics

Background:

  • Sarcoplasmic reticulum (SR) calcium content ([Ca]SRT) is crucial for normal cardiac function and electrophysiology.
  • Pathological alterations in [Ca]SRT contribute to heart failure and arrhythmias.
  • Intra-SR free calcium ([Ca]SR) regulates SR calcium release and cardiac excitation-contraction coupling.

Purpose of the Study:

  • To discuss methods for measuring [Ca]SR and [Ca]SRT.
  • To explain how [Ca]SR regulates calcium release.
  • To explore the role of calcium diffusion within the SR and its impact on cardiac function.

Main Methods:

  • Review of experimental measurements of [Ca]SR and [Ca]SRT.
  • Discussion of mathematical models simulating SR calcium dynamics.
  • Analysis of calcium diffusion within the SR network.

Main Results:

  • [Ca]SR dictates [Ca]SRT and controls the gating of calcium release channels.
  • [Ca]SR regulates the activation and termination of calcium release during excitation-contraction coupling.
  • Calcium diffusion within the SR can stabilize local [Ca]SR, but diffusion restrictions can cause spatial inhomogeneities.

Conclusions:

  • Accurate measurement and modeling of [Ca]SR dynamics are essential for understanding cardiac function and pathology.
  • Further research is needed to resolve existing controversies and advance our understanding of SR calcium handling.
  • Insights into SR calcium dynamics can inform therapeutic strategies for cardiovascular diseases.

Related Concept Videos

Feedback Regulation of Calcium Concentration01:27

Feedback 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...
Smooth Muscle Contraction01:25

Smooth 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...
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.
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.
Specialized Characteristics of Cardiac Muscles01:27

Specialized Characteristics of Cardiac Muscles

The primary role of cardiac muscles is to propel blood throughout the cardiovascular system. The cardiac muscle cells, or cardiomyocytes, exhibit specialized characteristics that allow them to perform this function.
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...
Excitation-Contraction Coupling in Skeletal Muscles01:20

Excitation-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...