View source for Cardiac muscle

{{Short description|Muscular tissue of heart in vertebrates}}
{{Infobox anatomy
| Name        = Cardiac muscle
| Latin       = textus muscularis striatus cardiacus
| Image       = Glanzstreifen.jpg
|
| Image2      = 414c Cardiacmuscle.jpg
| Caption2    =
| part_of     = The [[Heart#Wall|heart wall]]
| System      =
}}

'''Cardiac muscle''' (also called '''heart muscle''' or '''myocardium''') is one of three types of [[vertebrate]] [[muscle tissue]]s, the others being [[skeletal muscle]] and [[smooth muscle]]. It is an involuntary, [[striated muscle]] that constitutes the main tissue of the [[Heart#Wall|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 disc]]s, and encased by [[collagen fibers]] and other substances that form the [[extracellular matrix]].

<!-- Physiology of how it works efficiently -->
Cardiac muscle [[Muscle contraction|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 [[myofilament]]s to slide past each other in a process called [[Muscle contraction#Excitation-contraction coupling|excitation-contraction coupling]].
<!-- Pathophysiology and its consequences -->
Diseases of the heart muscle known as [[Cardiomyopathy|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 ===
{{See|Heart#Structure}}
[[File:Blausen 0470 HeartWall.png|thumb|3D rendering showing thick myocardium within the heart wall.|233x233px]]
[[File:2006 Heart Musculature.jpg|thumb|Differently oriented cardiac muscle fibers.|232x232px]]
[[File:Cardiac Muscle.png|thumb|Cardiac muscle|229x229px]] [[File:Cardiac sarcomere structure.png|thumb|270x270px|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 [[Heart valve|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 [[Pericardium|epicardium]] which forms part of the [[pericardial sac]] that surrounds, protects, and lubricates the heart.<ref name=":5">{{Cite book|title=Last's anatomy : regional and applied.|last=S.|first=Sinnatamby, Chummy|date=2006|publisher=Elsevier/Churchill Livingstone|others=Last, R. J. (Raymond Jack)|isbn=978-0-443-10032-1|edition=11th|location=Edinburgh|oclc=61692701}}</ref>

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.<ref>{{Cite journal|last1=Stöhr|first1=Eric J.|last2=Shave|first2=Rob E.|last3=Baggish|first3=Aaron L.|last4=Weiner|first4=Rory B.|date=2016-09-01|title=Left ventricular twist mechanics in the context of normal physiology and cardiovascular disease: a review of studies using speckle tracking echocardiography|journal=American Journal of Physiology. Heart and Circulatory Physiology|volume=311|issue=3|pages=H633–644|doi=10.1152/ajpheart.00104.2016|issn=1522-1539|pmid=27402663|hdl=10369/9408|doi-access=free}}</ref>

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 [[Aorta#Ascending aorta|aortic root]] and lie on the outer or epicardial surface of the heart.  Blood is then drained away by the [[Coronary circulation|coronary veins]] into the [[right atrium]].<ref name=":5" />

=== Microanatomy ===
[[File:Myocardiocyte.png|thumb|Illustration of a cardiac muscle cell.|272x272px]]
[[File:A single cardiomyocyte beating, five days after purification from cell culture.ogv|thumb|An isolated cardiac muscle cell, beating|274x274px]]
Cardiac muscle cells (also called '''cardiomyocytes''') are the contractile [[myocyte]]s of the cardiac muscle. The cells are surrounded by an [[extracellular matrix]] produced by supporting [[fibroblast cells]]. Specialised modified cardiomyocytes known as [[pacemaker cell]]s, 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 junction]]s.<ref name=Campbell_473>{{cite book |author=Neil A. Campbell  |display-authors=etal |title=Biology : concepts & connections |url=https://archive.org/details/studycardforcamp00camp  |url-access=limited  |year=2006 |publisher=Pearson/Benjamin Cummings |location=San Francisco |isbn=0-13-193480-5 |pages=[https://archive.org/details/studycardforcamp00camp/page/n514 473] |edition=5th}}</ref> 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]].<ref>{{cite web | vauthors = Kashou AH, Basit H, Chhabra L | title = Physiology, Sinoatrial Node (SA Node) | publisher = StatPearls | date=January 2020 | url = https://www.ncbi.nlm.nih.gov/books/NBK459238/ | access-date = 10 May 2020 | pmid = 29083608}}</ref> 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 [[cardiac automaticity|spontaneously generate]] and send out [[Cardiac action potential|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.<ref>{{cite web|title=Anatomy and Physiology of the Heart|url=http://www.bem.fi/book/06/06.htm|access-date= }}</ref> 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.<ref name="Gray's 2016">{{cite book |last1=Standring |first1=Susan |title=Gray's anatomy: the anatomical basis of clinical practice |date=2016|publisher=Elsevier |location=Philadelphia |isbn=9780702052309 |page=139 |edition=Forty-first}}</ref>

The Purkinje fibers rapidly conduct electrical signals; [[coronary arteries]] to bring nutrients to the muscle cells, and [[Coronary circulation#Cardiac veins|veins]] and a [[capillary]] network to take away waste products.<ref name=":1">{{Cite book|title=Human histology|last=Stevens|first= Alan |date=1997|publisher=Mosby|others=Lowe JS|isbn=978-0723424857 |edition=2nd |location=London |oclc=35652355}}</ref>

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 [[Arrhythmia|abnormal heart rhythms]] such as [[ventricular fibrillation]].<ref>{{Cite book|title=The ESC textbook of cardiovascular medicine|date=2009|publisher=Oxford University Press|vauthors=Camm AJ, Lüscher TF, Serruys PW|isbn=9780199566990 |edition=2nd |location=Oxford |oclc=321015206}}</ref>

Viewed through a microscope, cardiac muscle cells are roughly rectangular, measuring 100–150μm by 30–40μm.<ref name=":0"/> Individual cardiac muscle cells are joined at their ends by [[intercalated disc]]s to form long fibers.  Each cell contains [[myofibril]]s, specialized protein contractile fibers of [[actin]] and [[myosin]] that slide past each other.  These are organized into [[sarcomere]]s, the fundamental contractile units of muscle cells.  The regular organization of myofibrils into sarcomeres gives cardiac muscle cells a striped or [[Striated muscle tissue|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 [[Sarcomere|A bands]] composed mainly of myosin.<ref name=":1" />

Cardiomyocytes contain [[T-tubule]]s, pouches of [[sarcolemma|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 [[Cell nucleus|nucleus]] (some may have two central nuclei), unlike skeletal muscle cells which contain [[Multinucleate|many nuclei]]. Cardiac muscle cells contain many [[Mitochondrion|mitochondria]] which provide the energy needed for the cell in the form of [[adenosine triphosphate]] (ATP), making them highly resistant to fatigue.<ref name=":0" /><ref name=":1" />

==== T-tubules ====
{{Main|T-tubules}}
[[T-tubule]]s 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.<ref name=":0" /> 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]].<ref>{{Cite journal|last1=Hong|first1=TingTing|last2=Shaw|first2=Robin M.|date=January 2017|title=Cardiac T-Tubule Microanatomy and Function|journal=Physiological Reviews|volume=97|issue=1|pages=227–252|doi=10.1152/physrev.00037.2015|issn=1522-1210|pmid=27881552|pmc=6151489}}</ref>

The functions of T-tubules include rapidly transmitting electrical impulses known as [[Cardiac action potential|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|excitation-contraction coupling]].<ref name=":0">{{Cite book|title=Excitation-contraction coupling and cardiac contractile force|last=M.|first=Bers, D.|date=2001|publisher=Kluwer Academic Publishers|isbn=978-0792371588|edition=2nd|location=Dordrecht|oclc=47659382}}</ref> They are also involved in mechano-electric feedback,<ref>{{Cite journal |last1=Quinn |first1=T. Alexander |last2=Kohl |first2=Peter |date=2021-01-01 |title=Cardiac Mechano-Electric Coupling: Acute Effects of Mechanical Stimulation on Heart Rate and Rhythm |journal=Physiological Reviews |language=en |volume=101 |issue=1 |pages=37–92 |doi=10.1152/physrev.00036.2019 |pmid=32380895 |s2cid=218554597 |issn=0031-9333|doi-access=free }}</ref> as evident from cell contraction induced T-tubular content exchange (advection-assisted diffusion),<ref>{{Cite journal |last1=Rog-Zielinska |first1=Eva A. |last2=Scardigli |first2=Marina |last3=Peyronnet |first3=Remi |last4=Zgierski-Johnston |first4=Callum M. |last5=Greiner |first5=Joachim |last6=Madl |first6=Josef |last7=O'Toole |first7=Eileen T. |last8=Morphew |first8=Mary |last9=Hoenger |first9=Andreas |last10=Sacconi |first10=Leonardo |last11=Kohl |first11=Peter |date=2021-01-22 |title=Beat-by-Beat Cardiomyocyte T-Tubule Deformation Drives Tubular Content Exchange |journal=Circulation Research |language=en |volume=128 |issue=2 |pages=203–215 |doi=10.1161/CIRCRESAHA.120.317266 |issn=0009-7330 |pmc=7834912 |pmid=33228470}}</ref> which was confirmed by confocal and 3D electron tomography observations.<ref>{{Cite journal |last1=Kohl |first1=Peter |last2=Greiner |first2=Joachim |last3=Rog-Zielinska |first3=Eva A. |date=2022-04-08 |title=Electron microscopy of cardiac 3D nanodynamics: form, function, future |url=https://www.nature.com/articles/s41569-022-00677-x |journal=Nature Reviews Cardiology |volume=19 |issue=9 |language=en |pages=607–619 |doi=10.1038/s41569-022-00677-x |pmid=35396547 |s2cid=248004338 |issn=1759-5010|url-access=subscription }}</ref>

==== Intercalated discs ====
{{Main|Intercalated disc}}

[[File:1020 Cardiac Muscle.jpg|thumb|350px|[[Intercalated disc]]s are part of the cardiac muscle cell [[sarcolemma]] and they contain [[gap junction]]s and [[desmosome]]s.]]
The cardiac syncytium is a network of cardiomyocytes connected by [[intercalated disc]]s 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.<ref name="MoiniMoini2011">{{cite book|author1=Jahangir Moini|author2=Professor of Allied Health Everest University Indialantic Florida Jahangir Moini|title=Anatomy and Physiology for Health Professionals|url=https://books.google.com/books?id=Z-QTQh1Fg8wC&pg=PA213|year=2011|publisher=Jones & Bartlett Publishers|isbn=978-1-4496-3414-8|pages=213–}}</ref> 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]].<ref name="Khurana2005">{{cite book|author=Khurana|title=Textbook Of Medical Physiology|url=https://books.google.com/books?id=M6vviWpZ0LsC&pg=PA247|year= 2005|publisher=Elsevier India|isbn=978-81-8147-850-4|pages=247}}</ref>

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|fascia adherens junctions]], the intermediate filament anchoring [[desmosomes]], and [[gap junctions]].<ref name="Zhao">{{cite journal |last1=Zhao |first1=G |last2=Qiu |first2=Y |last3=Zhang |first3=HM |last4=Yang |first4=D |title=Intercalated discs: cellular adhesion and signaling in heart health and diseases. |journal=Heart Failure Reviews |date=January 2019 |volume=24 |issue=1 |pages=115–132 |doi=10.1007/s10741-018-9743-7 |pmid=30288656|s2cid=52919432 }}</ref> 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]].<ref name="Zhao"/><ref>{{cite journal |vauthors=Franke WW, Borrmann CM, Grund C, Pieperhoff S |title=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 |journal=[[European Journal of Cell Biology|Eur. J. Cell Biol.]] |volume=85 |issue=2 |pages=69–82 |date=February 2006 |pmid=16406610 |doi=10.1016/j.ejcb.2005.11.003 }}</ref><ref>{{cite journal |vauthors=Goossens S, Janssens B, Bonné S |title=A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs |journal=J. Cell Sci. |volume=120 |issue=Pt 12 |pages=2126–2136 |date=June 2007 |pmid=17535849 |doi=10.1242/jcs.004713 |display-authors=etal|doi-access=free |hdl=1854/LU-374870 |hdl-access=free }}</ref><ref>{{cite journal |vauthors=Pieperhoff S, Barth M, Rickelt S, Franke WW |veditors=Mahoney MG, Müller EJ, Koch PJ |title=Desmosomes and Desmosomal Cadherin Function in Skin and Heart Diseases-Advancements in Basic and Clinical Research |journal=Dermatol Res Pract |volume=2010 |year=2010 |pmid=20885972 |pmc=2946574 |doi=10.1155/2010/725647 |pages=1–3 |doi-access=free }}</ref>

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.<ref>{{BUHistology|22501loa|inline=1}}</ref>

==== Fibroblasts ====
{{Main|Fibroblasts}}
Cardiac fibroblasts are vital supporting cells within cardiac muscle.  They are unable to provide forceful contractions like [[Cardiac muscle cell|cardiomyocytes]], but instead are largely responsible for creating and maintaining the extracellular matrix which surrounds the cardiomyocytes.<ref name=":1" />  Fibroblasts play a crucial role in responding to injury, such as a [[myocardial infarction]].  Following injury, fibroblasts can become activated and turn into [[myofibroblast]]s – cells which exhibit behaviour somewhere between a fibroblast (generating extracellular matrix) and a [[Smooth muscle tissue|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.<ref name=":2">{{Cite journal|last1=Ivey|first1=Malina J.|last2=Tallquist|first2=Michelle D.|date=2016-10-25|title=Defining the Cardiac Fibroblast|journal=Circulation Journal|volume=80|issue=11|pages=2269–2276|doi=10.1253/circj.CJ-16-1003|issn=1347-4820|pmc=5588900|pmid=27746422}}</ref>

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,<ref>{{Cite journal|last=Rohr|first=Stephan|date=June 2009|title=Myofibroblasts in diseased hearts: new players in cardiac arrhythmias?|journal=Heart Rhythm|volume=6|issue=6|pages=848–856|doi=10.1016/j.hrthm.2009.02.038|issn=1556-3871|pmid=19467515}}</ref> as originally shown in vitro in the 1960s,<ref>{{cite journal | last1=Goshima | first1=K. | last2=Tonomura | first2=Y. | title=Synchronized beating of embryonic mouse myocardial cells mediated by FL cells in monolayer culture | journal=Experimental Cell Research | volume=56 | issue=2–3 | date=1969 | doi=10.1016/0014-4827(69)90029-9 | pages=387–392 |pmid=5387911}}</ref> and ultimately confirmed in native cardiac tissue with the help of optogenetic techniques.<ref>{{Cite journal |last1=Quinn |first1=T. Alexander |last2=Camelliti |first2=Patrizia |last3=Rog-Zielinska |first3=Eva A. |last4=Siedlecka |first4=Urszula |last5=Poggioli |first5=Tommaso |last6=O'Toole |first6=Eileen T. |last7=Knöpfel |first7=Thomas |last8=Kohl |first8=Peter |date=2016-12-20 |title=Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics |journal=Proceedings of the National Academy of Sciences |language=en |volume=113 |issue=51 |pages=14852–14857 |doi=10.1073/pnas.1611184114 |issn=0027-8424 |pmc=5187735 |pmid=27930302|bibcode=2016PNAS..11314852Q |doi-access=free }}</ref> Other potential roles for fibroblasts include electrical insulation of the [[Electrical conduction system of the heart|cardiac conduction system]], and the ability to transform into other cell types including cardiomyocytes  and [[adipocyte]]s.<ref name=":2" />

==== Extracellular matrix ====
{{Main|Extracellular matrix}}The [[extracellular matrix]] (ECM) surrounds the cardiomyocyte and fibroblasts.  The ECM is composed of proteins including [[collagen]] and [[elastin]] along with [[polysaccharide]]s (sugar chains) known as [[glycosaminoglycan]]s.<ref name=":1" /> 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.{{cn|date=May 2025}}

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 [[glycoprotein]]s called [[integrin]]s.<ref>{{Cite journal|last1=Horn|first1=Margaux A.|last2=Trafford|first2=Andrew W.|date=April 2016|title=Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling|journal=Journal of Molecular and Cellular Cardiology|volume=93|pages=175–185|doi=10.1016/j.yjmcc.2015.11.005|issn=1095-8584|pmc=4945757|pmid=26578393}}</ref>

== 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.<ref>{{cite journal |last=Bergmann|first=O. |author2=Bhardwaj, R. D. |author3=Bernard, S. |author4=Zdunek, S. |author5=Barnabe-Heider, F. |author6=Walsh, S. |author7=Zupicich, J. |author8=Alkass, K. |author9=Buchholz, B. A. |author10=Druid, H. |author11=Jovinge, S. |author12=Frisen, J.|title=Evidence for cardiomyocyte renewal in humans|journal=Science|date=3 April 2009 |volume=324 |issue=5923 |pages=98–102 |doi=10.1126/science.1164680 |pmid=19342590 |pmc=2991140|bibcode=2009Sci...324...98B }}</ref> 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.<ref name="goktepe2010">{{cite journal |last=Göktepe |first=S |author2=Abilez, OJ |author3=Parker, KK |author4=Kuhl, E |title=A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis |journal=Journal of Theoretical Biology |date=2010-08-07 |volume=265 |issue=3 |pages=433–442 |pmid=20447409 |doi=10.1016/j.jtbi.2010.04.023|bibcode=2010JThBi.265..433G |hdl=11511/57545 |hdl-access=free }}</ref> The cardiomyocytes extend lengthwise but have the same diameter, resulting in ventricular dilation.  During heart pressure overload, cardiomyocytes grow through concentric hypertrophy.<ref name="goktepe2010" /> The cardiomyocytes grow larger in diameter but have the same length, resulting in heart wall thickening.

== Physiology ==
{{Main|Cardiac excitation-contraction coupling}}
{{Further|Autorhythmicity|Myocardial contractility}}
The physiology of cardiac muscle shares many similarities with that of [[skeletal striated muscle|skeletal muscle]].  The primary function of both muscle types is to contract, and in both cases, a contraction begins with a characteristic flow of [[ion]]s 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.<ref>{{cite web|last=Klabunde|first=Richard|title=Cardiovascular Physiology= Cardiac muscle Concept|url=http://www.cvphysiology.com/Arrhythmias/A009.htm|access-date= }}</ref><ref>{{cite web|title=Cells Alive: Pumping Myocytes|url=http://www.cellsalive.com/myocyte.htm|access-date= }}</ref>

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 channel]]s 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 [[myofilament]]s 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 [[Muscle contraction#Cross-bridge cycle|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 ===
[[File:Dogcardiacmuscle400.jpg|thumb|250px|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.<ref name="Bergmann">{{cite journal |vauthors=Bergmann O, Bhardwaj RD, Bernard S |title=Evidence for cardiomyocyte renewal in humans |journal=Science |volume=324 |issue=5923 |pages=98–102 |date=April 2009 |pmid=19342590 |pmc=2991140 |doi=10.1126/science.1164680 |bibcode=2009Sci...324...98B |display-authors=etal}}</ref> 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.<ref name="Bergmann"/>

One way that cardiomyocyte regeneration occurs is through the division of pre-existing cardiomyocytes during the normal aging process.<ref>{{cite journal |vauthors=Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, Wu TD, Guerguin-Kern JL, Lechene CP, Lee RT |title=Mammalian heart renewal by pre-existing cardiomyocytes |journal=Nature |volume=493 |issue=7432 |pages=433–436 |date=January 2013 |pmid=23222518 |pmc=3548046 |doi=10.1038/nature11682 |bibcode=2013Natur.493..433S }}</ref>

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 [[Hematopoietic stem cell|bone marrow stem cells]] were able to differentiate into cardiomyocytes, and could be used to treat [[heart failure]].<ref>{{cite journal |vauthors=Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel K, McKay R, Nadal-Ginard B, Bodine DM, Anversa P |title=Bone marrow cells regenerate infarcted myocardium |journal=Nature |volume=410 |issue=6829 |pages=701–705 |date=April 2001 |pmid=11287958  |doi=10.1038/35070587 |bibcode=2001Natur.410..701O |s2cid=4424399 }}</ref><ref>{{cite journal |vauthors=Bolli R, Chugh AR, D'Amario D, Loughran JH, Stoddard MF, Ikram S, et al. |title=Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial |journal=The Lancet |volume=378 |issue=9806  |pages=1847–1857 |pmid= 22088800  |doi=10.1016/S0140-6736(11)61590-0 |url= |pmc=3614010 |year=2011 }}{{Retracted|doi=10.1016/S0140-6736(19)30542-2|pmid=30894259|http://retractionwatch.com/2014/04/11/harvard-brigham-heart-researcher-under-investigation-earns-lancet-expression-of-concern/ ''Retraction Watch''|http://retractionwatch.com/2018/10/14/harvard-and-the-brigham-recommend-31-retractions-for-cardiac-stem-cell-work/ ''Retraction Watch''|intentional=yes}}</ref>
However, other teams were unable to replicate these findings, and many of the original studies were later [[Retractions in academic publishing|retracted]] for scientific fraud.<ref>{{cite journal |vauthors=Maliken B, Molkentin J |title=Undeniable Evidence That the Adult Mammalian Heart Lacks an Endogenous Regenerative Stem Cell |journal=Circulation |volume=138 |issue=8  |pages=806–808 |pmid=30359129 |pmc=6205190 |doi=10.1161/CIRCULATIONAHA.118.035186 |year=2018 }}</ref><ref>{{cite web | last=Kolata | first=Gina | title=He Promised to Restore Damaged Hearts. Harvard Says His Lab Fabricated Research. | website=The New York Times | date=2018-10-29 | url=https://www.nytimes.com/2018/10/29/health/dr-piero-anversa-harvard-retraction.html }}</ref>

=== Differences between atria and ventricles ===
[[File:2006 Heart Musculature.jpg|thumb|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.<ref>{{Cite journal|last1=Walden|first1=A. P.|last2=Dibb|first2=K. M.|last3=Trafford|first3=A. W.|date=April 2009|title=Differences in intracellular calcium homeostasis between atrial and ventricular myocytes|journal=Journal of Molecular and Cellular Cardiology|volume=46|issue=4|pages=463–473|doi=10.1016/j.yjmcc.2008.11.003|issn=1095-8584|pmid=19059414}}</ref> 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 ''I''<sub>K(UR)</sub> are highly specific to atrial cardiomyocytes, making them a potential target for treatments for [[atrial fibrillation]].<ref>{{Cite journal|last1=Ravens|first1=Ursula|last2=Wettwer|first2=Erich|date=2011-03-01|title=Ultra-rapid delayed rectifier channels: molecular basis and therapeutic implications|journal=Cardiovascular Research|volume=89|issue=4|pages=776–785|doi=10.1093/cvr/cvq398|issn=1755-3245|pmid=21159668|doi-access=free}}</ref>

== Clinical significance ==
{{Further|Cardiomyopathy}}
Diseases affecting cardiac muscle, known as [[cardiomyopathies]], are the leading cause of death in [[Developed country|developed countries]].<ref>{{Cite journal|last1=Lozano|first1=Rafael|last2=Naghavi|first2=Mohsen|last3=Foreman|first3=Kyle|last4=Lim|first4=Stephen|last5=Shibuya|first5=Kenji|last6=Aboyans|first6=Victor|last7=Abraham|first7=Jerry|last8=Adair|first8=Timothy|last9=Aggarwal|first9=Rakesh|date=2012-12-15|title=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|journal=Lancet|volume=380|issue=9859|pages=2095–2128|doi=10.1016/S0140-6736(12)61728-0|issn=1474-547X|pmid=23245604|pmc=10790329 |hdl=10536/DRO/DU:30050819|s2cid=1541253|url=https://zenodo.org/record/2557786|hdl-access=free}}</ref> The most common condition is [[coronary artery disease]], in which the [[Ischemia|blood supply to the heart is reduced]]. The [[coronary arteries]] become narrowed by [[atherosclerosis|the formation of atherosclerotic plaques]].<ref name=":3">{{Cite journal|last1=Kolh|first1=Philippe|last2=Windecker|first2=Stephan|last3=Alfonso|first3=Fernando|last4=Collet|first4=Jean-Philippe|last5=Cremer|first5=Jochen|last6=Falk|first6=Volkmar|last7=Filippatos|first7=Gerasimos|last8=Hamm|first8=Christian|last9=Head|first9=Stuart J.|date=October 2014|title=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)|journal=European Journal of Cardio-Thoracic Surgery|volume=46|issue=4|pages=517–592|doi=10.1093/ejcts/ezu366|issn=1873-734X|pmid=25173601|doi-access=free}}</ref> If these narrowings become severe enough to partially restrict blood flow, the syndrome of [[angina]] pectoris may occur.<ref name=":3" /> 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.<ref>{{Cite journal|last1=Smith|first1=Jennifer N.|last2=Negrelli|first2=Jenna M.|last3=Manek|first3=Megha B.|last4=Hawes|first4=Emily M.|last5=Viera|first5=Anthony J.|date=March 2015|title=Diagnosis and management of acute coronary syndrome: an evidence-based update|journal=Journal of the American Board of Family Medicine|volume=28|issue=2|pages=283–293|doi=10.3122/jabfm.2015.02.140189|issn=1558-7118|pmid=25748771|doi-access=free}}</ref> If the blockage is not relieved promptly by [[Thrombolysis|medication]], [[percutaneous coronary intervention]], or [[Coronary artery bypass surgery|surgery]], then a heart muscle region may become permanently scarred and damaged.<ref>{{Cite journal|last1=Roffi|first1=Marco|last2=Patrono|first2=Carlo|last3=Collet|first3=Jean-Philippe|last4=Mueller|first4=Christian|last5=Valgimigli|first5=Marco|last6=Andreotti|first6=Felicita|last7=Bax|first7=Jeroen J.|last8=Borger|first8=Michael A.|last9=Brotons|first9=Carlos|date=2016-01-14|title=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)|journal=European Heart Journal|volume=37|issue=3|pages=267–315|doi=10.1093/eurheartj/ehv320|issn=1522-9645|pmid=26320110|doi-access=free|hdl=10067/1526940151162165141|hdl-access=free}}</ref> Specific cardiomyopathies include: increased [[left ventricular mass]] ([[hypertrophic cardiomyopathy]]),<ref>{{Cite journal|last1=Liew|first1=Alphonsus C.|last2=Vassiliou|first2=Vassilios S.|last3=Cooper|first3=Robert|last4=Raphael|first4=Claire E.|date=2017-12-12|title=Hypertrophic Cardiomyopathy-Past, Present and Future|journal=Journal of Clinical Medicine|volume=6|issue=12|pages=118|doi=10.3390/jcm6120118|issn=2077-0383|pmc=5742807|pmid=29231893|doi-access=free}}</ref> abnormally large ([[dilated cardiomyopathy]]),<ref>{{Cite journal|last1=Japp|first1=Alan G.|last2=Gulati|first2=Ankur|last3=Cook|first3=Stuart A.|last4=Cowie|first4=Martin R.|last5=Prasad|first5=Sanjay K.|date=2016-06-28|title=The Diagnosis and Evaluation of Dilated Cardiomyopathy|journal=Journal of the American College of Cardiology|volume=67|issue=25|pages=2996–3010|doi=10.1016/j.jacc.2016.03.590|issn=1558-3597|pmid=27339497|doi-access=free|hdl=10044/1/45801|hdl-access=free}}</ref> or abnormally stiff ([[restrictive cardiomyopathy]]).<ref>{{Cite journal|last=Garcia|first=Mario J.|date=2016-05-03|title=Constrictive Pericarditis Versus Restrictive Cardiomyopathy?|journal=Journal of the American College of Cardiology|volume=67|issue=17|pages=2061–2076|doi=10.1016/j.jacc.2016.01.076|issn=1558-3597|pmid=27126534|doi-access=free}}</ref> Some of these conditions are caused by genetic mutations and can be inherited.<ref>{{Cite journal|last=Towbin|first=Jeffrey A.|date=2014|title=Inherited cardiomyopathies|journal=Circulation Journal|volume=78|issue=10|pages=2347–2356|issn=1347-4820|pmc=4467885|pmid=25186923|doi=10.1253/circj.CJ-14-0893}}</ref>

Heart muscle can also become damaged despite a normal blood supply. The heart muscle may become inflamed in a condition called [[myocarditis]],<ref>{{Cite journal|last=Cooper|first=Leslie T.|date=2009-04-09|title=Myocarditis|journal=The New England Journal of Medicine|volume=360|issue=15|pages=1526–1538|doi=10.1056/NEJMra0800028|issn=1533-4406|pmc=5814110|pmid=19357408}}</ref> most commonly caused by a viral infection<ref>{{Cite journal|last=Rose|first=Noel R.|date=July 2016|title=Viral myocarditis|journal=Current Opinion in Rheumatology|volume=28|issue=4|pages=383–389|doi=10.1097/BOR.0000000000000303|issn=1531-6963|pmc=4948180|pmid=27166925}}</ref> but sometimes caused by the body's own [[immune system]].<ref>{{Cite book|last1=Bracamonte-Baran|first1=William|last2=Čiháková|first2=Daniela|title=The Immunology of Cardiovascular Homeostasis and Pathology |chapter=Cardiac Autoimmunity: Myocarditis |series=Advances in Experimental Medicine and Biology |date=2017|volume=1003|pages=187–221|doi=10.1007/978-3-319-57613-8_10|issn=0065-2598|pmc=5706653|pmid=28667560|isbn=978-3-319-57611-4}}</ref> Heart muscle can also be damaged by drugs such as alcohol, long standing high blood pressure or [[hypertension]], or persistent abnormal [[Tachycardia-induced cardiomyopathy|heart racing]].<ref name=":4">{{Cite journal|last1=Ponikowski|first1=Piotr|last2=Voors|first2=Adriaan A.|last3=Anker|first3=Stefan D.|last4=Bueno|first4=Héctor|last5=Cleland|first5=John G. F.|last6=Coats|first6=Andrew J. S.|last7=Falk|first7=Volkmar|last8=González-Juanatey|first8=José Ramón|last9=Harjola|first9=Veli-Pekka|date=August 2016|title=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|journal=European Journal of Heart Failure|volume=18|issue=8|pages=891–975|doi=10.1002/ejhf.592|issn=1879-0844|pmid=27207191|hdl=2434/427148|s2cid=221675744|url=http://orbi.ulg.ac.be/handle/2268/205777|hdl-access=free}}</ref>
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]].<ref name=":4" />

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.<ref name="Baroldi">{{Cite book|url=https://books.google.com/books?id=7SxiDwAAQBAJ&q=Myocytolysis&pg=PA21|title=The Etiopathogenesis of Coronary Heart Disease: A Heretical Theory Based on Morphology, Second Edition|last=Baroldi|first=Giorgio|year=2004|publisher=CRC Press|isbn=9781498712811|pages=88|language=en}}</ref><ref name="Olsen" >{{Cite book|url=https://books.google.com/books?id=uUP8CAAAQBAJ&q=Myocytolysis+definition&pg=PA48|title=Atlas of Cardiovascular Pathology|last=Olsen|first=E. G.|year=2012|publisher=Springer Science & Business Media|isbn=9789400932098|pages=48|language=en}}</ref>

== See also ==
{{Commons}}
{{Anatomy-terms}}
* [[Frank–Starling law of the heart]]
* [[Nebulette]]
* [[Protein S100-A1]]
* [[Regional function of the heart]]
* [[List of distinct cell types in the adult human body]]

== References ==
{{Reflist|30em}}

== External links ==
* [http://www.histology-world.com/photoalbum/thumbnails.php?album=10 Cardiac muscle histology]

{{muscular system}}
{{Muscle tissue}}
{{Heart anatomy}}
{{Authority control}}

[[Category:Cardiac anatomy]]
[[Category:Muscular system]]
[[Category:Cardiac electrophysiology]]
[[Category:Muscle tissue]]
[[Category:Articles containing video clips]]
[[Category:Histology]]