Diad

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Within the muscle tissue of animals and humans, contraction and relaxation of the muscle cells (myocytes) is a highly regulated and rhythmic process. In cardiomyocytes, or cardiac muscle cells, muscular contraction takes place due to movement at a structure referred to as the diad, sometimes spelled "dyad." The dyad is the connection of transverse- tubules (t-tubules) and the junctional sarcoplasmic reticulum (jSR). [1] Like skeletal muscle contractions, Calcium (Ca2+) ions are required for polarization and depolarization through a voltage-gated calcium channel. The rapid influx of calcium into the cell signals for the cells to contract. When the calcium intake travels through an entire muscle, it will trigger a united muscular contraction. This process is known as excitation-contraction coupling. [2] This contraction pushes blood inside the heart and from the heart to other regions of the body.

Contents

Myocyte Anatomy

Cardiac muscle histology 400x Cardiac muscle histology 400x.jpg
Cardiac muscle histology 400x

Myocytes are incredibly specialized cells with only a select number of different organelle types. A myocyte is composed of multiple myofibrils, which contain the “contractile units” of the muscle known as a sarcomere. [3] These sarcomeres are arranged in adjacent formations along the myofibrils. Similarly to the plasma membrane of other cells, the sarcolemma protects and surrounds the myocytes. The two cellular components that perform the “sliding filament” contraction are myosin and actin, also referred to as the thick and thin filaments respectively [2] The striations viewed using microscopy of the cardiac muscle are a result of the contrast between the thick and thin filaments. The z-line defines the borders of each sarcomere and act as the connection point between the thin filaments. The t-tubules and sarcoplasmic reticulum are used in conjunction to receive and direct the calcium ions and cause contraction. Once contracted, the clear H-zone between the actin filaments disappears as the filaments move towards each other.

Cardiomyocytes are a particular form of myocyte, only present in heart tissue. Along with the basic myocyte elements, these cells also contain one to four nuclei and a large amount of Adenosine Triphosphate (ATP). [2] These additions aid in the heart's resistance to fatigue to consistently pump blood throughout the body to deliver oxygen. Most muscle cells contain a triad, which is a joining of 2 terminal cisternae of the sarcoplasmic reticulum and one t- tubule. However, cardiac muscle cells contain a diad, which is a linking of only one sarcoplasmic reticulum with its respective t-tubule. Another notable distinction between all muscle cells and cardiac muscle cells is the presence of intercalated discs. These tight connections between the cardiomyocytes allows for the accelerated sending of action potential signals to perform the rapid, rhythmic contraction of the heart muscle.

One of the most incredible attributes of cardiac muscle is the ability to automatically beat. This means that even when isolated, for example on a petri dish in an in- vitro setting, the tissue is able to contract and release. This is due to the presence of “pacemaker cells,” which originate from the sinoatrial node. This structure allows for spontaneous depolarization, sending signals throughout the tissue.

Transverse-tubules

Muscle Anatomy Blausen 0801 SkeletalMuscle.png
Muscle Anatomy

Within the sarcolemma of the myocyte, there are specific invaginations referred to as transverse- tubules. These structures attached to the sarcomere z-lines help to promote interaction between the extracellular space and the interior of the cell. [1] Connecting these tubules to the Z line allows for a closer range of excitation- contraction coupling within the cell. [1] Within the t-tubules, distinct ion channels and cellular proteins are present within the t- tubule bilayer that allow movement of calcium influx from the extracellular space into the myocyte to initiate depolarization and contraction. Once traveling through the t- tubules, the calcium arrives at the sarcoplasmic reticulum.

Sarcoplasmic Reticulum

Within the lumen of the cardiac myocyte, the sarcoplasmic reticulum serves as the area of controlling the amount of calcium influx into the interior of the cell. [4] After traveling through the t- tubule, the calcium is stored in the sarcoplasmic reticulum to maintain low concentration of calcium inside the lumen. Upon contraction of this muscle, the cell is depolarized and the calcium is released into the lumen to create the excitation-contraction coupling. Once the initial calcium is released, a wave of additional calcium is discharged from the sarcoplasmic reticulum to maintain the contraction integrity.

The tension felt in muscles from prolonged contraction can be attributed to extended release of calcium ions through the sarcoplasmic reticulum. By absorbing calcium ions after contraction, the sarcoplasmic reticulum can regulate muscle fatigue and prevent overuse damage within the body.

Voltage-Gated Calcium Channels

Voltage- gated calcium channels play a critical role in controlling the influx of calcium ions into the myocyte in response to the changing action potential of the sarcoplasmic membrane. [5] The increase in action potential of the cell indicates depolarization of the cell, directly opening the ion channels to cause muscular contraction. When the action potential decreases, the ion channels close, preventing any calcium influx and further muscular contraction. This fluctuation within the myocyte contributes to the rhythmic “pacemaking” of the cardiac tissue.

There are two classes of voltage- gated calcium channels, L- type and T- type. [5] L-type calcium channels are more commonly found in myocardial tissue throughout the heart whereas T-type calcium channels are more concentrated in the pacemaker cells of the sinoatrial node. These channels also have slightly different activation levels. The L- type responds to a more positive action potential while the T- type channels are triggered at a more negative action potential. Discrepancies and/ or malfunctioning of these gates can contribute to a number of cardiac conditions, such as bradycardia.

Cardiac Conditions Due to Diad Defects

Because the structural organization of the myocyte is very complex and specific, changes to their arrangement and/ or function can cause cardiac illnesses or defects. For example, a leading cause of heart failure can be attributed to the lack of t- tubule and sarcoplasmic reticulum junctions or a decreased distance between the structures. [6] This change in structure causes the excitation- coupling response in the myocyte to either lessen significantly or be completely diminished. Therefore, few to no heart contractions would take place causing heart failure. On the contrary, an increase in the distance of the junction can create an increased excitation- coupling response, shown in both hypertension and cardiomyopathy. [6] These conditions are proof that even the smallest changes in a complex structure can have long- range consequences.

Related Research Articles

The muscular system is an organ system consisting of skeletal, smooth, and cardiac muscle. It permits movement of the body, maintains posture, and circulates blood throughout the body. The muscular systems in vertebrates are controlled through the nervous system although some muscles can be completely autonomous. Together with the skeletal system in the human, it forms the musculoskeletal system, which is responsible for the movement of the body.

<span class="mw-page-title-main">Sarcomere</span> Repeating unit of a myofibril in a muscle cell

A sarcomere is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells which are formed during embryonic myogenesis. Muscle fibers contain numerous tubular myofibrils. Myofibrils are composed of repeating sections of sarcomeres, which appear under the microscope as alternating dark and light bands. Sarcomeres are composed of long, fibrous proteins as filaments that slide past each other when a muscle contracts or relaxes. The costamere is a different component that connects the sarcomere to the sarcolemma.

<span class="mw-page-title-main">Sarcoplasmic reticulum</span> Menbrane-bound structure in muscle cells for storing calcium

The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels are controlled tightly, and can be released into the cell when necessary and then removed from the cell.

<span class="mw-page-title-main">Cardiac muscle</span> Muscular tissue of heart in vertebrates

Cardiac muscle is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall and the inner layer, with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix.

<span class="mw-page-title-main">Muscle cell</span> Type of cell found in muscle tissue

A muscle cell, also known as a myocyte, is a mature contractile cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal, smooth, and cardiac (cardiomyocytes). A skeletal muscle cell is long and threadlike with many nuclei and is called a muscle fiber. Muscle cells develop from embryonic precursor cells called myoblasts.

<span class="mw-page-title-main">Striated muscle tissue</span> Muscle tissue with repeating functional units called sarcomeres

Striated muscle tissue is a muscle tissue that features repeating functional units called sarcomeres. The presence of sarcomeres manifests as a series of bands visible along the muscle fibers, which is responsible for the striated appearance observed in microscopic images of this tissue. There are two types of striated muscle:

<span class="mw-page-title-main">Cardiac action potential</span> Biological process in the heart

The cardiac action potential is a brief change in voltage across the cell membrane of heart cells. This is caused by the movement of charged atoms between the inside and outside of the cell, through proteins called ion channels. The cardiac action potential differs from action potentials found in other types of electrically excitable cells, such as nerves. Action potentials also vary within the heart; this is due to the presence of different ion channels in different cells.

<span class="mw-page-title-main">Muscle contraction</span> Activation of tension-generating sites in muscle

Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as when holding something heavy in the same position. The termination of muscle contraction is followed by muscle relaxation, which is a return of the muscle fibers to their low tension-generating state.

Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. These channels are slightly permeable to sodium ions, so they are also called Ca2+–Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions.

<span class="mw-page-title-main">T-tubule</span> Extensions in cell membrane of muscle fibres

T-tubules are extensions of the cell membrane that penetrate into the center of skeletal and cardiac muscle cells. With membranes that contain large concentrations of ion channels, transporters, and pumps, T-tubules permit rapid transmission of the action potential into the cell, and also play an important role in regulating cellular calcium concentration.

Myocardial contractility represents the innate ability of the heart muscle (cardiac muscle or myocardium) to contract. The ability to produce changes in force during contraction result from incremental degrees of binding between different types of tissue, that is, between filaments of myosin (thick) and actin (thin) tissue. The degree of binding depends upon the concentration of calcium ions in the cell. Within an in vivo intact heart, the action/response of the sympathetic nervous system is driven by precisely timed releases of a catecholamine, which is a process that determines the concentration of calcium ions in the cytosol of cardiac muscle cells. The factors causing an increase in contractility work by causing an increase in intracellular calcium ions (Ca++) during contraction.

<span class="mw-page-title-main">Myofilament</span> The two protein filaments of myofibrils in muscle cells

Myofilaments are the three protein filaments of myofibrils in muscle cells. The main proteins involved are myosin, actin, and titin. Myosin and actin are the contractile proteins and titin is an elastic protein. The myofilaments act together in muscle contraction, and in order of size are a thick one of mostly myosin, a thin one of mostly actin, and a very thin one of mostly titin.

Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular Ca2+ stores (e.g., endoplasmic reticulum or sarcoplasmic reticulum). Although CICR was first proposed for skeletal muscle in the 1970s, it is now known that CICR is unlikely to be the primary mechanism for activating SR calcium release. Instead, CICR is thought to be crucial for excitation-contraction coupling in cardiac muscle. It is now obvious that CICR is a widely occurring cellular signaling process present even in many non-muscle cells, such as in the insulin-secreting pancreatic beta cells, epithelium, and many other cells. Since CICR is a positive-feedback system, it has been of great interest to elucidate the mechanism(s) responsible for its termination.

A calcium spark is the microscopic release of calcium (Ca2+) from a store known as the sarcoplasmic reticulum (SR), located within muscle cells. This release occurs through an ion channel within the membrane of the SR, known as a ryanodine receptor (RyR), which opens upon activation. This process is important as it helps to maintain Ca2+ concentration within the cell. It also initiates muscle contraction in skeletal and cardiac muscles and muscle relaxation in smooth muscles. Ca2+ sparks are important in physiology as they show how Ca2+ can be used at a subcellular level, to signal both local changes, known as local control, as well as whole cell changes.

<span class="mw-page-title-main">L-type calcium channel</span> Family of transport proteins

The L-type calcium channel is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This channel has four isoforms: Cav1.1, Cav1.2, Cav1.3, and Cav1.4.

<span class="mw-page-title-main">Ryanodine receptor 2</span> Transport protein and coding gene in humans

Ryanodine receptor 2 (RYR2) is one of a class of ryanodine receptors and a protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 gene. In the process of cardiac calcium-induced calcium release, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.

<span class="mw-page-title-main">Terminal cisternae</span> Enlarged areas of the sarcoplasmic reticulum surrounding the transverse tubules

Terminal cisternae are enlarged areas of the sarcoplasmic reticulum surrounding the transverse tubules.

Cardiac physiology or heart function is the study of healthy, unimpaired function of the heart: involving blood flow; myocardium structure; the electrical conduction system of the heart; the cardiac cycle and cardiac output and how these interact and depend on one another.

Calcium buffering describes the processes which help stabilise the concentration of free calcium ions within cells, in a similar manner to how pH buffers maintain a stable concentration of hydrogen ions. The majority of calcium ions within the cell are bound to intracellular proteins, leaving a minority freely dissociated. When calcium is added to or removed from the cytoplasm by transport across the cell membrane or sarcoplasmic reticulum, calcium buffers minimise the effect on changes in cytoplasmic free calcium concentration by binding calcium to or releasing calcium from intracellular proteins. As a result, 99% of the calcium added to the cytosol of a cardiomyocyte during each cardiac cycle becomes bound to calcium buffers, creating a relatively small change in free calcium.

Cardiac excitation-contraction coupling (CardiacEC coupling) describes the series of events, from the production of an electrical impulse (action potential) to the contraction of muscles in the heart. This process is of vital importance as it allows for the heart to beat in a controlled manner, without the need for conscious input. EC coupling results in the sequential contraction of the heart muscles that allows blood to be pumped, first to the lungs (pulmonary circulation) and then around the rest of the body (systemic circulation) at a rate between 60 and 100 beats every minute, when the body is at rest. This rate can be altered, however, by nerves that work to either increase heart rate (sympathetic nerves) or decrease it (parasympathetic nerves), as the body's oxygen demands change. Ultimately, muscle contraction revolves around a charged atom (ion), calcium (Ca2+), which is responsible for converting the electrical energy of the action potential into mechanical energy (contraction) of the muscle. This is achieved in a region of the muscle cell, called the transverse tubule during a process known as calcium induced calcium release.

References

  1. 1 2 3 Lu, Fujiian; Pu, William, T. (July 13, 2020). "The architecture and function of cardiac dyads". Biophysical Reviews. 12 (4): 1007–1017. doi:10.1007/s12551-020-00729-x. PMC   7429583 . PMID   32661902.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. 1 2 3 Saxton, Anthony; Tariq, Muhammad Ali; Bordoni, Bruno (August 8, 2022). Anatomy, Thorax, Cardiac Muscle. Florida: StatPearls. PMID   30570976.
  3. Hampton, Lucinda. "Muscle Cells (Myocyte)". Physiopedia. Retrieved November 9, 2022.
  4. Encyclopædia Britannica (ed.). "Sarcoplasmic reticulum". Britannica.com. Britannica. Retrieved November 10, 2022.
  5. 1 2 Mesirca, Pietro; Torrente, Angelo G.; Mangoni, Matteo E. (February 2, 2015). "Functional role of voltage gated Ca2+ channels in heart automaticity". Frontiers in Physiology. 6. doi: 10.3389/fphys.2015.00019 . PMC   4313592 .
  6. 1 2 Zhang, Hai-Bo; Li, Rong-Chang; Xu, Ming; et al. (May 1, 2013). "Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure". Cardiovascular Research. 98 (2): 269–276. doi: 10.1093/cvr/cvt030 . PMID   23405000 . Retrieved November 10, 2022.