Cardiac muscle

Last updated
Cardiac muscle
Glanzstreifen.jpg
414c Cardiacmuscle.jpg
Details
Part ofThe heart wall
Identifiers
Latin textus muscularis striatus cardiacus
MeSH D009206
TA98 A12.1.06.001
TA2 3950
FMA 9462
Anatomical terminology

Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the other 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 (the pericardium) and the inner layer (the endocardium), 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.

Contents

Cardiac muscle contracts in a similar manner to skeletal muscle, although with some important differences. Electrical stimulation in the form of a cardiac action potential triggers the release of calcium from the cell's internal calcium store, the sarcoplasmic reticulum. The rise in calcium causes the cell's myofilaments to slide past each other in a process called excitation-contraction coupling. Diseases of the heart muscle known as cardiomyopathies are of major importance. These include ischemic conditions caused by a restricted blood supply to the muscle such as angina, and myocardial infarction.

Structure

Gross anatomy

3D rendering showing thick myocardium within the heart wall. Blausen 0470 HeartWall.png
3D rendering showing thick myocardium within the heart wall.
Differently oriented cardiac muscle fibers. 2006 Heart Musculature.jpg
Differently oriented cardiac muscle fibers.
Cardiac muscle Cardiac Muscle.png
Cardiac muscle
Cardiac sarcomere structure Cardiac sarcomere structure.png
Cardiac sarcomere structure

Cardiac muscle tissue or myocardium forms the bulk of the heart. The heart wall is a three-layered structure with a thick layer of myocardium sandwiched between the inner endocardium and the outer epicardium (also known as the visceral pericardium). The inner endocardium lines the cardiac chambers, covers the cardiac valves, and joins with the endothelium that lines the blood vessels that connect to the heart. On the outer aspect of the myocardium is the epicardium which forms part of the pericardial sac that surrounds, protects, and lubricates the heart. [1]

Within the myocardium, there are several sheets of cardiac muscle cells or cardiomyocytes. The sheets of muscle that wrap around the left ventricle closest to the endocardium are oriented perpendicularly to those closest to the epicardium. When these sheets contract in a coordinated manner they allow the ventricle to squeeze in several directions simultaneously – longitudinally (becoming shorter from apex to base), radially (becoming narrower from side to side), and with a twisting motion (similar to wringing out a damp cloth) to squeeze the maximum possible amount of blood out of the heart with each heartbeat. [2]

Contracting heart muscle uses a lot of energy, and therefore requires a constant flow of blood to provide oxygen and nutrients. Blood is brought to the myocardium by the coronary arteries. These originate from the aortic root and lie on the outer or epicardial surface of the heart. Blood is then drained away by the coronary veins into the right atrium. [1]

Microanatomy

Illustration of a cardiac muscle cell. Myocardiocyte.png
Illustration of a cardiac muscle cell.
An isolated cardiac muscle cell, beating

Cardiac muscle cells (also called cardiomyocytes) are the contractile myocytes of the cardiac muscle. The cells are surrounded by an extracellular matrix produced by supporting fibroblast cells. Specialised modified cardiomyocytes known as pacemaker cells, set the rhythm of the heart contractions. The pacemaker cells are only weakly contractile without sarcomeres, and are connected to neighboring contractile cells via gap junctions. [3] They are located in the sinoatrial node (the primary pacemaker) positioned on the wall of the right atrium, near the entrance of the superior vena cava. [4] Other pacemaker cells are found in the atrioventricular node (secondary pacemaker).

Pacemaker cells carry the impulses that are responsible for the beating of the heart. They are distributed throughout the heart and are responsible for several functions. First, they are responsible for being able to spontaneously generate and send out electrical impulses. They also must be able to receive and respond to electrical impulses from the brain. Lastly, they must be able to transfer electrical impulses from cell to cell. [5] Pacemaker cells in the sinoatrial node, and atrioventricular node are smaller and conduct at a relatively slow rate between the cells. Specialized conductive cells in the bundle of His, and the Purkinje fibers are larger in diameter and conduct signals at a fast rate. [6]

The Purkinje fibers rapidly conduct electrical signals; coronary arteries to bring nutrients to the muscle cells, and veins and a capillary network to take away waste products. [7]

Cardiac muscle cells are the contracting cells that allow the heart to pump. Each cardiomyocyte needs to contract in coordination with its neighboring cells - known as a functional syncytium - working to efficiently pump blood from the heart, and if this coordination breaks down then – despite individual cells contracting – the heart may not pump at all, such as may occur during abnormal heart rhythms such as ventricular fibrillation. [8]

Viewed through a microscope, cardiac muscle cells are roughly rectangular, measuring 100–150μm by 30–40μm. [9] Individual cardiac muscle cells are joined at their ends by intercalated discs to form long fibers. Each cell contains myofibrils, specialized protein contractile fibers of actin and myosin that slide past each other. These are organized into sarcomeres, the fundamental contractile units of muscle cells. The regular organization of myofibrils into sarcomeres gives cardiac muscle cells a striped or striated appearance when looked at through a microscope, similar to skeletal muscle. These striations are caused by lighter I bands composed mainly of actin, and darker A bands composed mainly of myosin. [7]

Cardiomyocytes contain T-tubules, pouches of cell membrane that run from the cell surface to the cell's interior which help to improve the efficiency of contraction. The majority of these cells contain only one nucleus (some may have two central nuclei), unlike skeletal muscle cells which contain many nuclei. Cardiac muscle cells contain many mitochondria which provide the energy needed for the cell in the form of adenosine triphosphate (ATP), making them highly resistant to fatigue. [9] [7]

T-tubules

T-tubules are microscopic tubes that run from the cell surface to deep within the cell. They are continuous with the cell membrane, are composed of the same phospholipid bilayer, and are open at the cell surface to the extracellular fluid that surrounds the cell. T-tubules in cardiac muscle are bigger and wider than those in skeletal muscle, but fewer in number. [9] In the centre of the cell they join, running into and along the cell as a transverse-axial network. Inside the cell they lie close to the cell's internal calcium store, the sarcoplasmic reticulum. Here, a single tubule pairs with part of the sarcoplasmic reticulum called a terminal cisterna in a combination known as a diad. [10]

The functions of T-tubules include rapidly transmitting electrical impulses known as action potentials from the cell surface to the cell's core, and helping to regulate the concentration of calcium within the cell in a process known as excitation-contraction coupling. [9] They are also involved in mechano-electric feedback, [11] as evident from cell contraction induced T-tubular content exchange (advection-assisted diffusion), [12] which was confirmed by confocal and 3D electron tomography observations. [13]

Intercalated discs

Intercalated discs are part of the cardiac muscle cell sarcolemma and they contain gap junctions and desmosomes. 1020 Cardiac Muscle.jpg
Intercalated discs are part of the cardiac muscle cell sarcolemma and they contain gap junctions and desmosomes.

The cardiac syncytium is a network of cardiomyocytes connected by intercalated discs that enable the rapid transmission of electrical impulses through the network, enabling the syncytium to act in a coordinated contraction of the myocardium. There is an atrial syncytium and a ventricular syncytium that are connected by cardiac connection fibres. [14] Electrical resistance through intercalated discs is very low, thus allowing free diffusion of ions. The ease of ion movement along cardiac muscle fibers axes is such that action potentials are able to travel from one cardiac muscle cell to the next, facing only slight resistance. Each syncytium obeys the all or none law. [15]

Intercalated discs are complex adhering structures that connect the single cardiomyocytes to an electrochemical syncytium (in contrast to the skeletal muscle, which becomes a multicellular syncytium during embryonic development). The discs are responsible mainly for force transmission during muscle contraction. Intercalated discs consist of three different types of cell-cell junctions: the actin filament anchoring fascia adherens junctions, the intermediate filament anchoring desmosomes, and gap junctions. [16] They allow action potentials to spread between cardiac cells by permitting the passage of ions between cells, producing depolarization of the heart muscle. The three types of junction act together as a single area composita. [16] [17] [18] [19]

Under light microscopy, intercalated discs appear as thin, typically dark-staining lines dividing adjacent cardiac muscle cells. The intercalated discs run perpendicular to the direction of muscle fibers. Under electron microscopy, an intercalated disc's path appears more complex. At low magnification, this may appear as a convoluted electron dense structure overlying the location of the obscured Z-line. At high magnification, the intercalated disc's path appears even more convoluted, with both longitudinal and transverse areas appearing in longitudinal section. [20]

Fibroblasts

Cardiac fibroblasts are vital supporting cells within cardiac muscle. They are unable to provide forceful contractions like cardiomyocytes, but instead are largely responsible for creating and maintaining the extracellular matrix which surrounds the cardiomyocytes. [7] Fibroblasts play a crucial role in responding to injury, such as a myocardial infarction. Following injury, fibroblasts can become activated and turn into myofibroblasts – cells which exhibit behaviour somewhere between a fibroblast (generating extracellular matrix) and a smooth muscle cell (ability to contract). In this capacity, fibroblasts can repair an injury by creating collagen while gently contracting to pull the edges of the injured area together. [21]

Fibroblasts are smaller but more numerous than cardiomyocytes, and several fibroblasts can be attached to a cardiomyocyte at once. When attached to a cardiomyocyte they can influence the electrical currents passing across the muscle cell's surface membrane, and in the context are referred to as being electrically coupled, [22] as originally shown in vitro in the 1960s, [23] and ultimately confirmed in native cardiac tissue with the help of optogenetic techniques. [24] Other potential roles for fibroblasts include electrical insulation of the cardiac conduction system, and the ability to transform into other cell types including cardiomyocytes and adipocytes. [21]

Extracellular matrix

The extracellular matrix (ECM) surrounds the cardiomyocyte and fibroblasts. The ECM is composed of proteins including collagen and elastin along with polysaccharides (sugar chains) known as glycosaminoglycans. [7] Together, these substances give support and strength to the muscle cells, create elasticity in cardiac muscle, and keep the muscle cells hydrated by binding water molecules.

The matrix in immediate contact with the muscle cells is referred to as the basement membrane, mainly composed of type IV collagen and laminin. Cardiomyocytes are linked to the basement membrane via specialised glycoproteins called integrins. [25]

Development

Humans are born with a set number of heart muscle cells, or cardiomyocytes, which increase in size as the heart grows larger during childhood development. Evidence suggests that cardiomyocytes are slowly turned over during aging, but less than 50% of the cardiomyocytes present at birth are replaced during a normal life span. [26] The growth of individual cardiomyocytes not only occurs during normal heart development, it also occurs in response to extensive exercise (athletic heart syndrome), heart disease, or heart muscle injury such as after a myocardial infarction. A healthy adult cardiomyocyte has a cylindrical shape that is approximately 100μm long and 10–25μm in diameter. Cardiomyocyte hypertrophy occurs through sarcomerogenesis, the creation of new sarcomere units in the cell. During heart volume overload, cardiomyocytes grow through eccentric hypertrophy. [27] The cardiomyocytes extend lengthwise but have the same diameter, resulting in ventricular dilation. During heart pressure overload, cardiomyocytes grow through concentric hypertrophy. [27] The cardiomyocytes grow larger in diameter but have the same length, resulting in heart wall thickening.

Physiology

The physiology of cardiac muscle shares many similarities with that of skeletal muscle. The primary function of both muscle types is to contract, and in both cases, a contraction begins with a characteristic flow of ions across the cell membrane known as an action potential. The cardiac action potential subsequently triggers muscle contraction by increasing the concentration of calcium within the cytosol.

Cardiac cycle

The cardiac cycle is the performance of the human heart from the beginning of one heartbeat to the beginning of the next. It consists of two periods: one during which the heart muscle relaxes and refills with blood, called diastole, following a period of robust contraction and pumping of blood, dubbed systole. After emptying, the heart immediately relaxes and expands to receive another influx of blood returning from the lungs and other systems of the body, before again contracting to pump blood to the lungs and those systems. A normally performing heart must be fully expanded before it can efficiently pump again.

The rest phase is considered polarized. The resting potential during this phase of the beat separates the ions such as sodium, potassium, and calcium. Myocardial cells possess the property of automaticity or spontaneous depolarization. This is the direct result of a membrane which allows sodium ions to slowly enter the cell until the threshold is reached for depolarization. Calcium ions follow and extend the depolarization even further. Once calcium stops moving inward, potassium ions move out slowly to produce repolarization. The very slow repolarization of the CMC membrane is responsible for the long refractory period. [28] [29]

However, the mechanism by which calcium concentrations within the cytosol rise differ between skeletal and cardiac muscle. In cardiac muscle, the action potential comprises an inward flow of both sodium and calcium ions. The flow of sodium ions is rapid but very short-lived, while the flow of calcium is sustained and gives the plateau phase characteristic of cardiac muscle action potentials. The comparatively small flow of calcium through the L-type calcium channels triggers a much larger release of calcium from the sarcoplasmic reticulum in a phenomenon known as calcium-induced calcium release. In contrast, in skeletal muscle, minimal calcium flows into the cell during action potential and instead the sarcoplasmic reticulum in these cells is directly coupled to the surface membrane. This difference can be illustrated by the observation that cardiac muscle fibers require calcium to be present in the solution surrounding the cell to contract, while skeletal muscle fibers will contract without extracellular calcium.

During contraction of a cardiac muscle cell, the long protein myofilaments oriented along the length of the cell slide over each other in what is known as the sliding filament theory. There are two kinds of myofilaments, thick filaments composed of the protein myosin, and thin filaments composed of the proteins actin, troponin and tropomyosin. As the thick and thin filaments slide past each other the cell becomes shorter and fatter. In a mechanism known as cross-bridge cycling, calcium ions bind to the protein troponin, which along with tropomyosin then uncover key binding sites on actin. Myosin, in the thick filament, can then bind to actin, pulling the thick filaments along the thin filaments. When the concentration of calcium within the cell falls, troponin and tropomyosin once again cover the binding sites on actin, causing the cell to relax.

Regeneration

Dog cardiac muscle (400X) Dogcardiacmuscle400.jpg
Dog cardiac muscle (400X)

It was commonly believed that cardiac muscle cells could not be regenerated. However, this was contradicted by a report published in 2009. [30] Olaf Bergmann and his colleagues at the Karolinska Institute in Stockholm tested samples of heart muscle from people born before 1955 who had very little cardiac muscle around their heart, many showing with disabilities from this abnormality. By using DNA samples from many hearts, the researchers estimated that a 4-year-old renews about 20% of heart muscle cells per year, and about 69% of the heart muscle cells of a 50-year-old were generated after they were born. [30]

One way that cardiomyocyte regeneration occurs is through the division of pre-existing cardiomyocytes during the normal aging process. [31]

In the 2000s, the discovery of adult endogenous cardiac stem cells was reported, and studies were published that claimed that various stem cell lineages, including bone marrow stem cells were able to differentiate into cardiomyocytes, and could be used to treat heart failure. [32] [33] However, other teams were unable to replicate these findings, and many of the original studies were later retracted for scientific fraud. [34] [35]

Differences between atria and ventricles

The swirling musculature of the heart ensures effective pumping of blood. 2006 Heart Musculature.jpg
The swirling musculature of the heart ensures effective pumping of blood.

Cardiac muscle forms both the atria and the ventricles of the heart. Although this muscle tissue is very similar between cardiac chambers, some differences exist. The myocardium found in the ventricles is thick to allow forceful contractions, while the myocardium in the atria is much thinner. The individual myocytes that make up the myocardium also differ between cardiac chambers. Ventricular cardiomyocytes are longer and wider, with a denser T-tubule network. Although the fundamental mechanisms of calcium handling are similar between ventricular and atrial cardiomyocytes, the calcium transient is smaller and decays more rapidly in atrial myocytes, with a corresponding increase in calcium buffering capacity. [36] The complement of ion channels differs between chambers, leading to longer action potential durations and effective refractory periods in the ventricles. Certain ion currents such as IK(UR) are highly specific to atrial cardiomyocytes, making them a potential target for treatments for atrial fibrillation. [37]

Clinical significance

Diseases affecting cardiac muscle, known as cardiomyopathies, are the leading cause of death in developed countries. [38] The most common condition is coronary artery disease, in which the blood supply to the heart is reduced. The coronary arteries become narrowed by the formation of atherosclerotic plaques. [39] If these narrowings become severe enough to partially restrict blood flow, the syndrome of angina pectoris may occur. [39] This typically causes chest pain during exertion that is relieved by rest. If a coronary artery suddenly becomes very narrowed or completely blocked, interrupting or severely reducing blood flow through the vessel, a myocardial infarction or heart attack occurs. [40] If the blockage is not relieved promptly by medication, percutaneous coronary intervention, or surgery, then a heart muscle region may become permanently scarred and damaged. [41] Specific cardiomyopathies include: increased left ventricular mass (hypertrophic cardiomyopathy), [42] abnormally large (dilated cardiomyopathy), [43] or abnormally stiff (restrictive cardiomyopathy). [44] Some of these conditions are caused by genetic mutations and can be inherited. [45]

Heart muscle can also become damaged despite a normal blood supply. The heart muscle may become inflamed in a condition called myocarditis, [46] most commonly caused by a viral infection [47] but sometimes caused by the body's own immune system. [48] Heart muscle can also be damaged by drugs such as alcohol, long standing high blood pressure or hypertension, or persistent abnormal heart racing. [49] Many of these conditions, if severe enough, can damage the heart so much that the pumping function of the heart is reduced. If the heart is no longer able to pump enough blood to meet the body's needs, this is described as heart failure. [49]

Significant damage to cardiac muscle cells is referred to as myocytolysis which is considered a type of cellular necrosis defined as either coagulative or colliquative. [50] [51]

See also

Related Research Articles

<span class="mw-page-title-main">Premature ventricular contraction</span> Skipped beat with ventricular origin

A premature ventricular contraction (PVC) is a common event where the heartbeat is initiated by Purkinje fibers in the ventricles rather than by the sinoatrial node. PVCs may cause no symptoms or may be perceived as a "skipped beat" or felt as palpitations in the chest. PVCs do not usually pose any danger.

<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">Troponin</span> Protein complex

Troponin, or the troponin complex, is a complex of three regulatory proteins that are integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle. Measurements of cardiac-specific troponins I and T are extensively used as diagnostic and prognostic indicators in the management of myocarditis, myocardial infarction and acute coronary syndrome. Blood troponin levels may be used as a diagnostic marker for stroke or other myocardial injury that is ongoing, although the sensitivity of this measurement is low.

<span class="mw-page-title-main">Frank–Starling law</span> Relationship between stroke volume and end diastolic volume

The Frank–Starling law of the heart represents the relationship between stroke volume and end diastolic volume. The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles, before contraction, when all other factors remain constant. As a larger volume of blood flows into the ventricle, the blood stretches cardiac muscle, leading to an increase in the force of contraction. The Frank-Starling mechanism allows the cardiac output to be synchronized with the venous return, arterial blood supply and humoral length, without depending upon external regulation to make alterations. The physiological importance of the mechanism lies mainly in maintaining left and right ventricular output equality.

<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 conduction system</span> Aspect of heart function

The cardiac conduction system transmits the signals generated by the sinoatrial node – the heart's pacemaker, to cause the heart muscle to contract, and pump blood through the body's circulatory system. The pacemaking signal travels through the right atrium to the atrioventricular node, along the bundle of His, and through the bundle branches to Purkinje fibers in the walls of the ventricles. The Purkinje fibers transmit the signals more rapidly to stimulate contraction of the ventricles.

<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.

<span class="mw-page-title-main">Intercalated disc</span> Microscopic feature of cardiac muscle

Intercalated discs or lines of Eberth are microscopic identifying features of cardiac muscle. Cardiac muscle consists of individual heart muscle cells (cardiomyocytes) connected by intercalated discs to work as a single functional syncytium. By contrast, skeletal muscle consists of multinucleated muscle fibers and exhibits no intercalated discs. Intercalated discs support synchronized contraction of cardiac tissue in a wave-like pattern so that the heart can work like a pump. They occur at the Z line of the sarcomere and can be visualized easily when observing a longitudinal section of the tissue.

<span class="mw-page-title-main">Desmin</span> Mammalian protein found in humans

Desmin is a protein that in humans is encoded by the DES gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture.

<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.

<span class="mw-page-title-main">Takotsubo cardiomyopathy</span> Sudden temporary weakening of the heart muscle

Takotsubo cardiomyopathy or takotsubo syndrome (TTS), also known as stress cardiomyopathy, is a type of non-ischemic cardiomyopathy in which there is a sudden temporary weakening of the muscular portion of the heart. It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called broken heart syndrome.

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). 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. This contraction pushes blood inside the heart and from the heart to other regions of the body.

<span class="mw-page-title-main">Muscle</span> Basic biological tissue

Muscle is a soft tissue, one of the four basic types of animal tissue. Muscle tissue gives skeletal muscles the ability to contract. Muscle is formed during embryonic development, in a process known as myogenesis. Muscle tissue contains special contractile proteins called actin and myosin which interact to cause movement. Among many other muscle proteins present are two regulatory proteins, troponin and tropomyosin.

<span class="mw-page-title-main">TNNT2</span> Protein-coding gene in the species Homo sapiens

Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

<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">S100A1</span> Protein-coding gene in the species Homo sapiens

Protein S100-A1, also known as S100 calcium-binding protein A1 is a protein which in humans is encoded by the S100A1 gene. S100A1 is highly expressed in cardiac and skeletal muscle, and localizes to Z-discs and sarcoplasmic reticulum. S100A1 has shown promise as an effective candidate for gene therapy to treat post-myocardially infarcted cardiac tissue.

<span class="mw-page-title-main">Troponin C type 1</span> Protein-coding gene in the species Homo sapiens

Troponin C, also known as TN-C or TnC, is a protein that resides in the troponin complex on actin thin filaments of striated muscle and is responsible for binding calcium to activate muscle contraction. Troponin C is encoded by the TNNC1 gene in humans for both cardiac and slow skeletal muscle.

<span class="mw-page-title-main">DSC2</span> Protein-coding gene in humans

Desmocollin-2 is a protein that in humans is encoded by the DSC2 gene. Desmocollin-2 is a cadherin-type protein that functions to link adjacent cells together in specialized regions known as desmosomes. Desmocollin-2 is widely expressed, and is the only desmocollin isoform expressed in cardiac muscle, where it localizes to intercalated discs. Mutations in DSC2 have been causally linked to arrhythmogenic right ventricular cardiomyopathy.

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.

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 S., Sinnatamby, Chummy (2006). Last's anatomy : regional and applied. Last, R. J. (Raymond Jack) (11th ed.). Edinburgh: Elsevier/Churchill Livingstone. ISBN   978-0-443-10032-1. OCLC   61692701.{{cite book}}: CS1 maint: multiple names: authors list (link)
  2. ↑ Stöhr, Eric J.; Shave, Rob E.; Baggish, Aaron L.; Weiner, Rory B. (2016-09-01). "Left ventricular twist mechanics in the context of normal physiology and cardiovascular disease: a review of studies using speckle tracking echocardiography". American Journal of Physiology. Heart and Circulatory Physiology. 311 (3): H633–644. doi: 10.1152/ajpheart.00104.2016 . hdl:10369/9408. ISSN   1522-1539. PMID   27402663.
  3. ↑ Neil A. Campbell; et al. (2006). Biology : concepts & connections (5th ed.). San Francisco: Pearson/Benjamin Cummings. pp.  473. ISBN   0-13-193480-5.
  4. ↑ Kashou AH, Basit H, Chhabra L (January 2020). "Physiology, Sinoatrial Node (SA Node)". StatPearls. PMID   29083608 . Retrieved 10 May 2020.{{cite journal}}: Cite journal requires |journal= (help)
  5. ↑ "Anatomy and Physiology of the Heart".
  6. ↑ Standring, Susan (2016). Gray's anatomy : the anatomical basis of clinical practice (Forty-first ed.). [Philadelphia]. p. 139. ISBN   9780702052309.{{cite book}}: CS1 maint: location missing publisher (link)
  7. 1 2 3 4 5 (Pathologist), Stevens, Alan (1997). Human histology. Lowe, J. S. (James Steven), Stevens, Alan (Pathologist). (2nd ed.). London: Mosby. ISBN   978-0723424857. OCLC   35652355.{{cite book}}: CS1 maint: multiple names: authors list (link)
  8. ↑ The ESC textbook of cardiovascular medicine. Camm, A. John., Lüscher, Thomas F. (Thomas Felix), Serruys, P. W., European Society of Cardiology (2nd ed.). Oxford: Oxford University Press. 2009. ISBN   9780199566990. OCLC   321015206.{{cite book}}: CS1 maint: others (link)
  9. 1 2 3 4 M., Bers, D. (2001). Excitation-contraction coupling and cardiac contractile force (2nd ed.). Dordrecht: Kluwer Academic Publishers. ISBN   978-0792371588. OCLC   47659382.{{cite book}}: CS1 maint: multiple names: authors list (link)
  10. ↑ Hong, TingTing; Shaw, Robin M. (January 2017). "Cardiac T-Tubule Microanatomy and Function". Physiological Reviews. 97 (1): 227–252. doi:10.1152/physrev.00037.2015. ISSN   1522-1210. PMC   6151489 . PMID   27881552.
  11. ↑ Quinn, T. Alexander; Kohl, Peter (2021-01-01). "Cardiac Mechano-Electric Coupling: Acute Effects of Mechanical Stimulation on Heart Rate and Rhythm". Physiological Reviews. 101 (1): 37–92. doi: 10.1152/physrev.00036.2019 . ISSN   0031-9333. PMID   32380895. S2CID   218554597.
  12. ↑ Rog-Zielinska, Eva A.; Scardigli, Marina; Peyronnet, Remi; Zgierski-Johnston, Callum M.; Greiner, Joachim; Madl, Josef; O’Toole, Eileen T.; Morphew, Mary; Hoenger, Andreas; Sacconi, Leonardo; Kohl, Peter (2021-01-22). "Beat-by-Beat Cardiomyocyte T-Tubule Deformation Drives Tubular Content Exchange". Circulation Research. 128 (2): 203–215. doi:10.1161/CIRCRESAHA.120.317266. ISSN   0009-7330. PMC   7834912 . PMID   33228470.
  13. ↑ Kohl, Peter; Greiner, Joachim; Rog-Zielinska, Eva A. (2022-04-08). "Electron microscopy of cardiac 3D nanodynamics: form, function, future". Nature Reviews Cardiology. 19 (9): 607–619. doi:10.1038/s41569-022-00677-x. ISSN   1759-5010. PMID   35396547. S2CID   248004338.
  14. ↑ Jahangir Moini; Professor of Allied Health Everest University Indialantic Florida Jahangir Moini (2011). Anatomy and Physiology for Health Professionals. Jones & Bartlett Publishers. pp. 213–. ISBN   978-1-4496-3414-8.
  15. ↑ Khurana (2005). Textbook Of Medical Physiology. Elsevier India. p. 247. ISBN   978-81-8147-850-4.
  16. 1 2 Zhao, G; Qiu, Y; Zhang, HM; Yang, D (January 2019). "Intercalated discs: cellular adhesion and signaling in heart health and diseases". Heart Failure Reviews. 24 (1): 115–132. doi:10.1007/s10741-018-9743-7. PMID   30288656. S2CID   52919432.
  17. ↑ Franke WW, Borrmann CM, Grund C, Pieperhoff S (February 2006). "The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins". Eur. J. Cell Biol. 85 (2): 69–82. doi:10.1016/j.ejcb.2005.11.003. PMID   16406610.
  18. ↑ Goossens S, Janssens B, Bonné S, et al. (June 2007). "A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs". J. Cell Sci. 120 (Pt 12): 2126–2136. doi: 10.1242/jcs.004713 . hdl: 1854/LU-374870 . PMID   17535849.
  19. ↑ Pieperhoff S, Barth M, Rickelt S, Franke WW (2010). Mahoney MG, Müller EJ, Koch PJ (eds.). "Desmosomes and Desmosomal Cadherin Function in Skin and Heart Diseases-Advancements in Basic and Clinical Research". Dermatol Res Pract. 2010: 1–3. doi: 10.1155/2010/725647 . PMC   2946574 . PMID   20885972.
  20. ↑ Histology image:22501loa from Vaughan, Deborah (2002). A Learning System in Histology: CD-ROM and Guide. Oxford University Press. ISBN   978-0195151732.
  21. 1 2 Ivey, Malina J.; Tallquist, Michelle D. (2016-10-25). "Defining the Cardiac Fibroblast". Circulation Journal. 80 (11): 2269–2276. doi:10.1253/circj.CJ-16-1003. ISSN   1347-4820. PMC   5588900 . PMID   27746422.
  22. ↑ Rohr, Stephan (June 2009). "Myofibroblasts in diseased hearts: new players in cardiac arrhythmias?". Heart Rhythm. 6 (6): 848–856. doi:10.1016/j.hrthm.2009.02.038. ISSN   1556-3871. PMID   19467515.
  23. ↑ Goshima, K.; Tonomura, Y. (1969). "Synchronized beating of embryonic mouse myocardial cells mediated by FL cells in monolayer culture". Experimental Cell Research. 56 (2–3): 387–392. doi:10.1016/0014-4827(69)90029-9. PMID   5387911.
  24. ↑ Quinn, T. Alexander; Camelliti, Patrizia; Rog-Zielinska, Eva A.; Siedlecka, Urszula; Poggioli, Tommaso; O'Toole, Eileen T.; Knöpfel, Thomas; Kohl, Peter (2016-12-20). "Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics". Proceedings of the National Academy of Sciences. 113 (51): 14852–14857. Bibcode:2016PNAS..11314852Q. doi: 10.1073/pnas.1611184114 . ISSN   0027-8424. PMC   5187735 . PMID   27930302.
  25. ↑ Horn, Margaux A.; Trafford, Andrew W. (April 2016). "Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling". Journal of Molecular and Cellular Cardiology. 93: 175–185. doi:10.1016/j.yjmcc.2015.11.005. ISSN   1095-8584. PMC   4945757 . PMID   26578393.
  26. ↑ Bergmann, O.; Bhardwaj, R. D.; Bernard, S.; Zdunek, S.; Barnabe-Heider, F.; Walsh, S.; Zupicich, J.; Alkass, K.; Buchholz, B. A.; Druid, H.; Jovinge, S.; Frisen, J. (3 April 2009). "Evidence for cardiomyocyte renewal in humans". Science. 324 (5923): 98–102. Bibcode:2009Sci...324...98B. doi:10.1126/science.1164680. PMC   2991140 . PMID   19342590.
  27. 1 2 Göktepe, S; Abilez, OJ; Parker, KK; Kuhl, E (2010-08-07). "A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis". Journal of Theoretical Biology. 265 (3): 433–442. Bibcode:2010JThBi.265..433G. doi:10.1016/j.jtbi.2010.04.023. PMID   20447409.
  28. ↑ Klabunde, Richard. "Cardiovascular Physiology= Cardiac muscle Concept".
  29. ↑ "Cells Alive: Pumping Myocytes".
  30. 1 2 Bergmann O, Bhardwaj RD, Bernard S, et al. (April 2009). "Evidence for cardiomyocyte renewal in humans". Science. 324 (5923): 98–102. Bibcode:2009Sci...324...98B. doi:10.1126/science.1164680. PMC   2991140 . PMID   19342590.
  31. ↑ Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, Wu TD, Guerguin-Kern JL, Lechene CP, Lee RT (January 2013). "Mammalian heart renewal by pre-existing cardiomyocytes". Nature. 493 (7432): 433–436. Bibcode:2013Natur.493..433S. doi:10.1038/nature11682. PMC   3548046 . PMID   23222518.
  32. ↑ Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel K, McKay R, Nadal-Ginard B, Bodine DM, Anversa P (April 2001). "Bone marrow cells regenerate infarcted myocardium". Nature. 410 (6829): 701–705. Bibcode:2001Natur.410..701O. doi:10.1038/35070587. PMID   11287958. S2CID   4424399.
  33. ↑ Bolli R, Chugh AR, D'Amario D, Loughran JH, Stoddard MF, Ikram S, et al. (2011). "Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial". The Lancet. 378 (9806): 1847–1857. doi:10.1016/S0140-6736(11)61590-0. PMC   3614010 . PMID   22088800. (Retracted, see doi:10.1016/S0140-6736(19)30542-2, PMID   30894259,  Retraction Watch . If this is an intentional citation to a retracted paper, please replace {{ retracted |...}} with {{ retracted |...|intentional=yes}}.)
  34. ↑ Maliken B, Molkentin J (2018). "Undeniable Evidence That the Adult Mammalian Heart Lacks an Endogenous Regenerative Stem Cell". Circulation. 138 (8): 806–808. doi:10.1161/CIRCULATIONAHA.118.035186. PMC   6205190 . PMID   30359129.
  35. ↑ Kolata, Gina (2018-10-29). "He Promised to Restore Damaged Hearts. Harvard Says His Lab Fabricated Research". The New York Times.
  36. ↑ Walden, A. P.; Dibb, K. M.; Trafford, A. W. (April 2009). "Differences in intracellular calcium homeostasis between atrial and ventricular myocytes". Journal of Molecular and Cellular Cardiology. 46 (4): 463–473. doi:10.1016/j.yjmcc.2008.11.003. ISSN   1095-8584. PMID   19059414.
  37. ↑ Ravens, Ursula; Wettwer, Erich (2011-03-01). "Ultra-rapid delayed rectifier channels: molecular basis and therapeutic implications". Cardiovascular Research. 89 (4): 776–785. doi: 10.1093/cvr/cvq398 . ISSN   1755-3245. PMID   21159668.
  38. ↑ Lozano, Rafael; Naghavi, Mohsen; Foreman, Kyle; Lim, Stephen; Shibuya, Kenji; Aboyans, Victor; Abraham, Jerry; Adair, Timothy; Aggarwal, Rakesh (2012-12-15). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–2128. doi:10.1016/S0140-6736(12)61728-0. hdl: 10536/DRO/DU:30050819 . ISSN   1474-547X. PMC   10790329 . PMID   23245604. S2CID   1541253.
  39. 1 2 Kolh, Philippe; Windecker, Stephan; Alfonso, Fernando; Collet, Jean-Philippe; Cremer, Jochen; Falk, Volkmar; Filippatos, Gerasimos; Hamm, Christian; Head, Stuart J. (October 2014). "2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI)". European Journal of Cardio-Thoracic Surgery. 46 (4): 517–592. doi: 10.1093/ejcts/ezu366 . ISSN   1873-734X. PMID   25173601.
  40. ↑ Smith, Jennifer N.; Negrelli, Jenna M.; Manek, Megha B.; Hawes, Emily M.; Viera, Anthony J. (March 2015). "Diagnosis and management of acute coronary syndrome: an evidence-based update". Journal of the American Board of Family Medicine. 28 (2): 283–293. doi: 10.3122/jabfm.2015.02.140189 . ISSN   1558-7118. PMID   25748771.
  41. ↑ Roffi, Marco; Patrono, Carlo; Collet, Jean-Philippe; Mueller, Christian; Valgimigli, Marco; Andreotti, Felicita; Bax, Jeroen J.; Borger, Michael A.; Brotons, Carlos (2016-01-14). "2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)". European Heart Journal. 37 (3): 267–315. doi: 10.1093/eurheartj/ehv320 . hdl: 10067/1526940151162165141 . ISSN   1522-9645. PMID   26320110.
  42. ↑ Liew, Alphonsus C.; Vassiliou, Vassilios S.; Cooper, Robert; Raphael, Claire E. (2017-12-12). "Hypertrophic Cardiomyopathy-Past, Present and Future". Journal of Clinical Medicine. 6 (12): 118. doi: 10.3390/jcm6120118 . ISSN   2077-0383. PMC   5742807 . PMID   29231893.
  43. ↑ Japp, Alan G.; Gulati, Ankur; Cook, Stuart A.; Cowie, Martin R.; Prasad, Sanjay K. (2016-06-28). "The Diagnosis and Evaluation of Dilated Cardiomyopathy". Journal of the American College of Cardiology. 67 (25): 2996–3010. doi: 10.1016/j.jacc.2016.03.590 . hdl: 10044/1/45801 . ISSN   1558-3597. PMID   27339497.
  44. ↑ Garcia, Mario J. (2016-05-03). "Constrictive Pericarditis Versus Restrictive Cardiomyopathy?". Journal of the American College of Cardiology. 67 (17): 2061–2076. doi: 10.1016/j.jacc.2016.01.076 . ISSN   1558-3597. PMID   27126534.
  45. ↑ Towbin, Jeffrey A. (2014). "Inherited cardiomyopathies". Circulation Journal. 78 (10): 2347–2356. doi:10.1253/circj.CJ-14-0893. ISSN   1347-4820. PMC   4467885 . PMID   25186923.
  46. ↑ Cooper, Leslie T. (2009-04-09). "Myocarditis". The New England Journal of Medicine. 360 (15): 1526–1538. doi:10.1056/NEJMra0800028. ISSN   1533-4406. PMC   5814110 . PMID   19357408.
  47. ↑ Rose, Noel R. (July 2016). "Viral myocarditis". Current Opinion in Rheumatology. 28 (4): 383–389. doi:10.1097/BOR.0000000000000303. ISSN   1531-6963. PMC   4948180 . PMID   27166925.
  48. ↑ Bracamonte-Baran, William; Čiháková, Daniela (2017). "Cardiac Autoimmunity: Myocarditis". The Immunology of Cardiovascular Homeostasis and Pathology. Advances in Experimental Medicine and Biology. Vol. 1003. pp. 187–221. doi:10.1007/978-3-319-57613-8_10. ISBN   978-3-319-57611-4. ISSN   0065-2598. PMC   5706653 . PMID   28667560.
  49. 1 2 Ponikowski, Piotr; Voors, Adriaan A.; Anker, Stefan D.; Bueno, Héctor; Cleland, John G. F.; Coats, Andrew J. S.; Falk, Volkmar; González-Juanatey, José Ramón; Harjola, Veli-Pekka (August 2016). "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC". European Journal of Heart Failure. 18 (8): 891–975. doi:10.1002/ejhf.592. hdl: 2434/427148 . ISSN   1879-0844. PMID   27207191. S2CID   221675744.
  50. ↑ Baroldi, Giorgio (2004). The Etiopathogenesis of Coronary Heart Disease: A Heretical Theory Based on Morphology, Second Edition. CRC Press. p. 88. ISBN   9781498712811.
  51. ↑ Olsen, E. G. (2012). Atlas of Cardiovascular Pathology. Springer Science & Business Media. p. 48. ISBN   9789400932098.
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