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Smooth muscle is an involuntary non- striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit muscle, the whole bundle or sheet of smooth muscle cells contracts as a syncytium. Smooth muscle is found in the walls of hollow organs, including the stomach, intestines,
bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine en ...
and
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
; in the walls of passageways, such as
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
, and lymph vessels, and in the tracts of the respiratory, urinary, and reproductive
systems A system is a group of interacting or interrelated elements that act according to a set of rules to form a unified whole. A system, surrounded and influenced by its environment, is described by its boundaries, structure and purpose and expresse ...
. In the eyes, the ciliary muscles, a type of smooth muscle, dilate and contract the iris and alter the shape of the lens. In the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
, smooth muscle cells such as those of the arrector pili cause hair to stand erect in response to cold temperature or
fear Fear is an intensely unpleasant emotion in response to perceiving or recognizing a danger or threat. Fear causes physiological changes that may produce behavioral reactions such as mounting an aggressive response or fleeing the threat. Fear ...
.


Structure


Gross anatomy

Smooth muscle is grouped into two types: single-unit smooth muscle, also known as visceral smooth muscle, and multiunit smooth muscle. Most smooth muscle is of the single-unit type, and is found in the walls of most internal organs (viscera); and lines blood vessels (except large elastic arteries), the urinary tract, and the digestive tract. It is not found in the heart which has cardiac muscle. In single-unit smooth muscle a single cell in a bundle is innervated by an autonomic nerve fiber (myogenic). An action potential can be propagated through neighbouring muscle cells due to the presence of many gap junctions between the cells. Due to this property, single-unit bundles form a syncytium that contracts in a coordinated fashion making the whole muscle contract or relax. (such as the uterine muscles during childbirth). Single-unit visceral smooth muscle is myogenic; it can contract regularly without input from a motor neuron (as opposed to multiunit smooth muscle, which is neurogenic - that is, its contraction must be initiated by an autonomic nervous system neuron). A few of the cells in a given single unit may behave as pacemaker cells, generating rhythmic action potentials due to their intrinsic electrical activity. Because of its myogenic nature, single-unit smooth muscle is usually active, even when it's not receiving any neural stimulation. Multiunit smooth muscle is found in the
trachea The trachea, also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air- breathing animals with lungs. The trachea extends from t ...
, the iris of the eye, and lining the large elastic arteries. However, the terms single- and multi-unit smooth muscle represents an oversimplification. This is due to the fact that smooth muscles for the most part are controlled and influenced by a combination of different neural elements. In addition, it has been observed that most of the time there will be some cell to cell communication and activators/ inhibitors produced locally. This leads to a somewhat coordinated response even in multiunit smooth muscle. Smooth muscle differs from
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...
and
cardiac muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) 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 ...
in terms of structure, function, regulation of contraction, and excitation-contraction coupling. However, smooth muscle tissue tends to demonstrate greater elasticity and function within a larger length-tension curve than striated muscle. This ability to stretch and still maintain contractility is important in organs like the intestines and urinary bladder. Smooth muscle in the gastrointestinal tract is activated by a composite of three types of cells – smooth muscle cells (SMCs), interstitial cells of Cajal (ICCs), and
platelet-derived growth factor receptor alpha PDGFRA, i.e. platelet-derived growth factor receptor A, also termed PDGFRα, i.e. platelet-derived growth factor receptor α, or CD140a i.e. Cluster of Differentiation 140a, is a receptor located on the surface of a wide range of cell types. This r ...
(PDGFRα) that are electrically coupled and work together as an SIP functional syncytium.


Microanatomy


Smooth muscle cells

A smooth muscle cell is a spindle-shaped myocyte with a wide middle and tapering ends, and a single nucleus. Like striated muscle, smooth muscle can tense and relax. In the relaxed state, each cell is 30–200 micrometers in length, some thousands of times shorter than a
skeletal muscle cell Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
. There are no
myofibril A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as muscle fibers, and these cells contain many chains of myofibrils. Each myofi ...
s present but much of the cytoplasm is taken up by the proteins of myosin and
actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
which together have the capability to contract.p. 174
in: ''The vascular smooth muscle cell: molecular and biological responses to the extracellular matrix''. Authors: Stephen M. Schwartz, Robert P. Mecham. Editors: Stephen M. Schwartz, Robert P. Mecham. Contributors: Stephen M. Schwartz, Robert P. Mecham. Publisher: Academic Press, 1995.


Myosin

Myosin is primarily class II in smooth muscle. * Myosin II contains two ''heavy chains'' (MHC) which constitute the head and tail domains. Each of these heavy chains contains the N-terminal head domain, while the C-terminal tails take on a
coiled-coil A coiled coil is a structural motif in proteins in which 2–7 alpha-helices are coiled together like the strands of a rope. (Dimers and trimers are the most common types.) Many coiled coil-type proteins are involved in important biological f ...
morphology, holding the two heavy chains together (imagine two snakes wrapped around each other, such as in a caduceus). Thus, myosin II has two heads. In smooth muscle, there is a single gene (
MYH11 Myosin-11 is a protein that in humans is encoded by the ''MYH11'' gene. Function Myosin-11 is a smooth muscle myosin belonging to the myosin heavy chain family. Myosin-11 is a subunit of a hexameric protein that consists of two heavy chain s ...
) that codes for the heavy chains myosin II, but there are splice variants of this gene that result in four distinct isoforms. Also, smooth muscle may contain MHC that is not involved in contraction, and that can arise from multiple genes. * Myosin II also contains 4 ''light chains'' (MLC), resulting in 2 per head, weighing 20 (MLC20) and 17 (MLC17) kDa. These bind the heavy chains in the "neck" region between the head and tail. ** The MLC20 is also known as the ''regulatory light chain'' and actively participates in
muscle contraction 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 a ...
. Two MLC20 isoforms are found in smooth muscle, and they are encoded by different genes, but only one isoform participates in contraction. ** The MLC17 is also known as the ''essential light chain''. Its exact function is unclear, but it's believed that it contributes to the structural stability of the myosin head along with MLC20. Two variants of MLC17 (MLC17a/b) exist as a result of alternative splicing at the MLC17 gene. Different combinations of heavy and light chains allow for up to hundreds of different types of myosin structures, but it is unlikely that more than a few such combinations are actually used or permitted within a specific smooth muscle bed. In the uterus, a shift in myosin expression has been hypothesized to avail for changes in the directions of uterine contractions that are seen during the menstrual cycle.


Actin

The thin filaments that are part of the contractile machinery are predominantly composed of alpha-actin and gamma-actin. Smooth muscle alpha-actin is the predominant isoform within smooth muscle. There is also a lot of actin (mainly beta-actin) that does not take part in contraction, but that polymerizes just below the plasma membrane in the presence of a contractile stimulant and may thereby assist in mechanical tension. Alpha-actin is also expressed as distinct genetic isoforms such as smooth muscle, cardiac muscle and skeletal muscle specific isoforms of alpha-actin. The ratio of
actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
to myosin is between 2:1 and 10:1 in smooth muscle. Conversely, from a mass ratio standpoint (as opposed to a molar ratio), myosin is the dominant protein in striated skeletal muscle with the actin to myosin ratio falling in the 1:2 to 1:3 range. A typical value for healthy young adults is 1:2.2.


Other associated proteins

Smooth muscle does not contain the protein troponin; instead calmodulin (which takes on the regulatory role in smooth muscle), caldesmon and calponin are significant proteins expressed within smooth muscle. *
Tropomyosin Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons. Tropomyosin and the actin skeleton All organisms contain organelles that provide physical integrity to their cells. These type of organelles ...
is present in smooth muscle, spanning seven actin monomers and is laid out end to end over the entire length of the thin filaments. In striated muscle, tropomyosin serves to block actin–myosin interactions until calcium is present, but in smooth muscle, its function is unknown. * Calponin molecules may exist in equal number as actin, and has been proposed to be a load-bearing protein. * Caldesmon has been suggested to be involved in tethering actin, myosin and tropomyosin, and thereby enhance the ability of smooth muscle to maintain tension. Also, all three of these proteins may have a role in inhibiting the ATPase activity of the myosin complex that otherwise provides energy to fuel muscle contraction.


Dense bodies

The actin filaments are attached to dense bodies, which are analogous to the Z-discs in striated muscle sarcomeres. Dense bodies are rich in alpha-actinin (α-actinin), and also attach intermediate filaments (consisting largely of vimentin and desmin), and thereby appear to serve as anchors from which the thin filaments can exert force. Dense bodies also are associated with beta-actin, which is the type found in the cytoskeleton, suggesting that dense bodies may coordinate tensions from both the contractile machinery and the cytoskeleton. Dense bodies appear darker under an electron microscope, and so they are sometimes described as electron dense. The intermediate filaments are connected to other intermediate filaments via dense bodies, which eventually are attached to adherens junctions (also called focal adhesions) in the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
of the smooth muscle cell, called the sarcolemma. The adherens junctions consist of large number of proteins including alpha-actinin (α-actinin), vinculin and cytoskeletal actin. The adherens junctions are scattered around ''dense bands'' that are circumfering the smooth muscle cell in a rib-like pattern. The dense band (or dense plaques) areas alternate with regions of membrane containing numerous caveolae. When complexes of actin and myosin contract, force is transduced to the sarcolemma through intermediate filaments attaching to such dense bands.


Contraction

During contraction, there is a spatial reorganization of the contractile machinery to optimize force development. part of this reorganization consists of vimentin being phosphorylated at Ser56 by a
p21 activated kinase p21 activated kinases (PAKs) are members of a family of enzymes. They serve as targets for the small GTP binding proteins CDC42 and Rac and have been implicated in a wide range of biological activities. Members include: * PAK1, regulating cell ...
, resulting in some disassembly of vimentin polymers. Also, the number of myosin filaments is dynamic between the relaxed and contracted state in some tissues as the ratio of actin to myosin changes, and the length and number of myosin filaments change. Isolated single smooth muscle cells have been observed contracting in a spiral corkscrew fashion, and isolated permeabilized smooth muscle cells adhered to glass (so contractile proteins allowed to internally contract) demonstrate zones of contractile protein interactions along the long axis as the cell contracts. Smooth muscle-containing tissue needs to be stretched often, so elasticity is an important attribute of smooth muscle. Smooth muscle cells may secrete a complex extracellular matrix containing collagen (predominantly types I and III),
elastin Elastin is a protein that in humans is encoded by the ''ELN'' gene. Elastin is a key component of the extracellular matrix in gnathostomes (jawed vertebrates). It is highly elastic and present in connective tissue allowing many tissues in the bo ...
, glycoproteins, and proteoglycans. Smooth muscle also has specific elastin and collagen receptors to interact with these proteins of the extracellular matrix. These fibers with their extracellular matrices contribute to the viscoelasticity of these tissues. For example, the great arteries are viscolelastic vessels that act like a Windkessel, propagating ventricular contraction and smoothing out the pulsatile flow, and the smooth muscle within the
tunica media The tunica media ( New Latin "middle coat"), or media for short, is the middle tunica (layer) of an artery or vein. It lies between the tunica intima on the inside and the tunica externa on the outside. Artery Tunica media is made up of smooth ...
contributes to this property.


Caveolae

The sarcolemma also contains caveolae, which are microdomains of lipid rafts specialized to
cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
events and ion channels. These invaginations in the sarcoplasm contain a host of receptors ( prostacyclin, endothelin, serotonin, muscarinic receptors, adrenergic receptors), second messenger generators ( adenylate cyclase, phospholipase C), G proteins (RhoA, G alpha), kinases ( rho kinase-ROCK, protein kinase C, protein Kinase A), ion channels (L type
calcium channels A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables ex ...
, ATP sensitive potassium channels, calcium sensitive potassium channels) in close proximity. The caveolae are often close to sarcoplasmic reticulum or mitochondria, and have been proposed to organize signaling molecules in the membrane.


Excitation-contraction coupling

A smooth muscle is excited by external stimuli, which causes contraction. Each step is further detailed below.


Inducing stimuli and factors

Smooth muscle may contract spontaneously (via
ionic channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
dynamics) or as in the gut special pacemakers cells interstitial cells of Cajal produce rhythmic contractions. Also, contraction, as well as relaxation, can be induced by a number of physiochemical agents (e.g., hormones, drugs, neurotransmitters – particularly from the autonomic nervous system). Smooth muscle in various regions of the vascular tree, the airway and lungs, kidneys and vagina is different in their expression of ionic channels, hormone receptors, cell-signaling pathways, and other proteins that determine function.


External substances

For instance, blood vessels in skin, gastrointestinal system, kidney and brain respond to
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...
and epinephrine (from sympathetic stimulation or the adrenal medulla) by producing vasoconstriction (this response is mediated through
alpha-1 adrenergic receptors alpha-1 (α1) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the Gq heterotrimeric G protein. α1-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α1A-, α1B-, and α1D-adrenergic ...
). However, blood vessels within skeletal muscle and cardiac muscle respond to these
catecholamines A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a subs ...
producing vasodilation because they possess beta-
adrenergic receptors The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like bet ...
. So there is a difference in the distribution of the various adrenergic receptors that explains the difference in why blood vessels from different areas respond to the same agent norepinephrine/epinephrine differently as well as differences due to varying amounts of these catecholamines that are released and sensitivities of various receptors to concentrations. Generally, arterial smooth muscle responds to carbon dioxide by producing vasodilation, and responds to oxygen by producing vasoconstriction. Pulmonary blood vessels within the lung are unique as they vasodilate to high oxygen tension and vasoconstrict when it falls. Bronchiole, smooth muscle that line the airways of the lung, respond to high carbon dioxide producing vasodilation and vasoconstrict when carbon dioxide is low. These responses to carbon dioxide and oxygen by pulmonary blood vessels and bronchiole airway smooth muscle aid in matching perfusion and ventilation within the lungs. Further different smooth muscle tissues display extremes of abundant to little sarcoplasmic reticulum so excitation-contraction coupling varies with its dependence on intracellular or extracellular calcium. Recent research indicates that sphingosine-1-phosphate (S1P) signaling is an important regulator of vascular smooth muscle contraction. When transmural pressure increases,
sphingosine kinase 1 Sphingosine kinase 1 is an enzyme that in humans is encoded by the ''SPHK1'' gene. Sphingosine kinase 1 phosphorylates sphingosine to sphingosine-1-phosphate (S1P) SK1 is normally a cytosolic protein but is recruited to membranes rich in phosp ...
phosphorylates sphingosine to S1P, which binds to the S1P2 receptor in plasma membrane of cells. This leads to a transient increase in intracellular calcium, and activates Rac and Rhoa signaling pathways. Collectively, these serve to increase MLCK activity and decrease MLCP activity, promoting muscle contraction. This allows arterioles to increase resistance in response to increased blood pressure and thus maintain constant blood flow. The Rhoa and Rac portion of the signaling pathway provides a calcium-independent way to regulate
resistance artery A resistance artery is small diameter blood vessel in the microcirculation that contributes significantly to the creation of the resistance to flow and regulation of blood flow. Resistance arteries are usually small arteries or arterioles and inclu ...
tone.


Spread of impulse

To maintain organ dimensions against force, cells are fastened to one another by adherens junctions. As a consequence, cells are mechanically coupled to one another such that contraction of one cell invokes some degree of contraction in an adjoining cell. Gap junctions couple adjacent cells chemically and electrically, facilitating the spread of chemicals (e.g., calcium) or action potentials between smooth muscle cells. Single unit smooth muscle displays numerous gap junctions and these tissues often organize into sheets or bundles which contract in bulk.


Contraction

Smooth muscle contraction is caused by the sliding of myosin and
actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
filaments (a sliding filament mechanism) over each other. The energy for this to happen is provided by the
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysi ...
of ATP. Myosin functions as an ATPase utilizing ATP to produce a molecular conformational change of part of the myosin and produces movement. Movement of the filaments over each other happens when the globular heads protruding from myosin filaments attach and interact with actin filaments to form crossbridges. The myosin heads tilt and drag along the actin filament a small distance (10–12 nm). The heads then release the actin filament and then changes angle to relocate to another site on the actin filament a further distance (10–12 nm) away. They can then re-bind to the actin molecule and drag it along further. This process is called crossbridge cycling and is the same for all muscles (see
muscle contraction 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 a ...
). Unlike cardiac and skeletal muscle, smooth muscle does not contain the calcium-binding protein troponin. Contraction is initiated by a calcium-regulated phosphorylation of myosin, rather than a calcium-activated troponin system. Crossbridge cycling causes contraction of myosin and actin complexes, in turn causing increased tension along the entire chains of tensile structures, ultimately resulting in contraction of the entire smooth muscle tissue.


Phasic or tonic

Smooth muscle may contract phasically with rapid contraction and relaxation, or tonically with slow and sustained contraction. The reproductive, digestive, respiratory, and urinary tracts, skin, eye, and vasculature all contain this tonic muscle type. This type of smooth muscle can maintain force for prolonged time with only little energy utilization. There are differences in the myosin heavy and light chains that also correlate with these differences in contractile patterns and kinetics of contraction between tonic and phasic smooth muscle.


Activation of myosin heads

Crossbridge cycling cannot occur until the myosin heads have been activated to allow crossbridges to form. When the light chains are phosphorylated, they become active and will allow contraction to occur. The enzyme that phosphorylates the light chains is called
myosin light-chain kinase Myosin light-chain kinase also known as MYLK or MLCK is a serine/threonine-specific protein kinase that phosphorylates a specific myosin light chain, namely, the regulatory light chain of myosin II. General structural features While there ar ...
(MLCK), also called MLC20 kinase. In order to control contraction, MLCK will work only when the muscle is stimulated to contract. Stimulation will increase the intracellular concentration of calcium ions. These bind to a molecule called calmodulin, and form a calcium-calmodulin complex. It is this complex that will bind to MLCK to activate it, allowing the chain of reactions for contraction to occur. Activation consists of phosphorylation of a serine on position 19 (Ser19) on the MLC20 light chain, which causes a conformational change that increases the angle in the neck domain of the myosin heavy chain, which corresponds to the part of the cross-bridge cycle where the myosin head is unattached to the actin filament and relocates to another site on it. After attachment of the myosin head to the actin filament, this serine phosphorylation also activates the ATPase activity of the myosin head region to provide the energy to fuel the subsequent contraction. Phosphorylation of a threonine on position 18 (Thr18) on MLC20 is also possible and may further increase the ATPase activity of the myosin complex.


Sustained maintenance

Phosphorylation of the MLC20 myosin light chains correlates well with the shortening velocity of smooth muscle. During this period there is a rapid burst of energy utilization as measured by oxygen consumption. Within a few minutes of initiation the calcium level markedly decrease, MLC20 myosin light chains phosphorylation decreases, and energy utilization decreases and the muscle can relax. Still, smooth muscle has the ability of sustained maintenance of force in this situation as well. This sustained phase has been attributed to certain myosin crossbridges, termed latch-bridges, that are cycling very slowly, notably slowing the progression to the cycle stage whereby dephosphorylated myosin detaches from the actin, thereby maintaining the force at low energy costs. This phenomenon is of great value especially for tonically active smooth muscle. Isolated preparations of vascular and visceral smooth muscle contract with depolarizing high potassium balanced saline generating a certain amount of contractile force. The same preparation stimulated in normal balanced saline with an agonist such as endothelin or serotonin will generate more contractile force. This increase in force is termed calcium sensitization. The myosin light chain phosphatase is inhibited to increase the gain or sensitivity of myosin light chain kinase to calcium. There are number of cell signalling pathways believed to regulate this decrease in myosin light chain phosphatase: a RhoA-Rock kinase pathway, a Protein kinase C-Protein kinase C potentiation
inhibitor protein The inhibitor protein (IP) is situated in the mitochondrial matrix and protects the cell against rapid ATP hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used ...
17 (CPI-17) pathway, telokin, and a Zip kinase pathway. Further Rock kinase and Zip kinase have been implicated to directly phosphorylate the 20kd myosin light chains.


Other contractile mechanisms

Other cell signaling pathways and protein kinases ( Protein kinase C, Rho kinase, Zip kinase, Focal adhesion kinases) have been implicated as well and actin polymerization dynamics plays a role in force maintenance. While myosin light chain phosphorylation correlates well with shortening velocity, other cell signaling pathways have been implicated in the development of force and maintenance of force. Notably the phosphorylation of specific tyrosine residues on the focal adhesion adapter protein-paxillin by specific tyrosine kinases has been demonstrated to be essential to force development and maintenance. For example, cyclic nucleotides can relax arterial smooth muscle without reductions in crossbridge phosphorylation, a process termed force suppression. This process is mediated by the phosphorylation of the small heat shock protein, hsp20, and may prevent phosphorylated myosin heads from interacting with actin.


Relaxation

The phosphorylation of the light chains by MLCK is countered by a myosin light-chain phosphatase, which dephosphorylates the MLC20 myosin light chains and thereby inhibits contraction. Other signaling pathways have also been implicated in the regulation actin and myosin dynamics. In general, the relaxation of smooth muscle is by cell-signaling pathways that increase the myosin phosphatase activity, decrease the intracellular calcium levels, hyperpolarize the smooth muscle, and/or regulate actin and myosin muscle can be mediated by the endothelium-derived relaxing factor-nitric oxide, endothelial derived hyperpolarizing factor (either an endogenous cannabinoid, cytochrome P450 metabolite, or hydrogen peroxide), or prostacyclin (PGI2). Nitric oxide and PGI2 stimulate soluble guanylate cyclase and membrane bound adenylate cyclase, respectively. The cyclic nucleotides (cGMP and cAMP) produced by these cyclases activate Protein Kinase G and Protein Kinase A and phosphorylate a number of proteins. The phosphorylation events lead to a decrease in intracellular calcium (inhibit L type Calcium channels, inhibits
IP3 receptor Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physio ...
channels, stimulates sarcoplasmic reticulum Calcium pump ATPase), a decrease in the 20kd myosin light chain phosphorylation by altering calcium sensitization and increasing myosin light chain phosphatase activity, a stimulation of calcium sensitive potassium channels which hyperpolarize the cell, and the phosphorylation of amino acid residue serine 16 on the small heat shock protein (hsp20)by Protein Kinases A and G. The phosphorylation of hsp20 appears to alter actin and focal adhesion dynamics and actin-myosin interaction, and recent evidence indicates that hsp20 binding to 14-3-3 protein is involved in this process. An alternative hypothesis is that phosphorylated Hsp20 may also alter the affinity of phosphorylated myosin with actin and inhibit contractility by interfering with crossbridge formation. The endothelium derived hyperpolarizing factor stimulates calcium sensitive potassium channels and/or ATP sensitive potassium channels and stimulate potassium efflux which hyperpolarizes the cell and produces relaxation.


Invertebrate smooth muscle

In invertebrate smooth muscle, contraction is initiated with the binding of calcium directly to myosin and then rapidly cycling cross-bridges, generating force. Similar to the mechanism of vertebrate smooth muscle, there is a low calcium and low energy utilization catch phase. This sustained phase or catch phase has been attributed to a catch protein that has similarities to myosin light-chain kinase and the elastic protein-titin called twitchin. Clams and other bivalve mollusks use this catch phase of smooth muscle to keep their shell closed for prolonged periods with little energy usage.


Specific effects

Although the structure and function is basically the same in smooth muscle cells in different organs, their specific effects or end-functions differ. The contractile function of vascular smooth muscle regulates the lumenal diameter of the small arteries-arterioles called resistance arteries, thereby contributing significantly to setting the level of blood pressure and blood flow to vascular beds. Smooth muscle contracts slowly and may maintain the contraction (tonically) for prolonged periods in blood vessels, bronchioles, and some sphincters. Activating arteriole smooth muscle can decrease the lumenal diameter 1/3 of resting so it drastically alters blood flow and resistance. Activation of aortic smooth muscle doesn't significantly alter the lumenal diameter but serves to increase the viscoelasticity of the vascular wall. In the digestive tract, smooth muscle contracts in a rhythmic
peristaltic Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, whic ...
fashion, rhythmically forcing foodstuffs through the digestive tract as the result of phasic contraction. A non-contractile function is seen in specialized smooth muscle within the afferent arteriole of the juxtaglomerular apparatus, which secretes
renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the ...
in response to osmotic and pressure changes, and also it is believed to secrete ATP in tubuloglomerular regulation of glomerular filtration rate. Renin in turn activates the
renin–angiotensin system The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance. When renal blood flow is reduced, ...
to regulate blood pressure.


Growth and rearrangement

The mechanism in which external factors stimulate growth and rearrangement is not yet fully understood. A number of growth factors and neurohumoral agents influence smooth muscle growth and differentiation. The Notch receptor and cell-signaling pathway have been demonstrated to be essential to vasculogenesis and the formation of arteries and veins. The proliferation is implicated in the pathogenesis of atherosclerosis and is inhibited by nitric oxide. The embryological origin of smooth muscle is usually of mesodermal origin, after the creation of muscle cells in a process known as myogenesis. However, the smooth muscle within the Aorta and Pulmonary arteries (the Great Arteries of the heart) is derived from ectomesenchyme of neural crest origin, although coronary artery smooth muscle is of mesodermal origin.


Related diseases

Multisystemic smooth muscle dysfunction syndrome Multisystemic smooth muscle dysfunction syndrome (MSMDS) is a genetic disorder caused by R179 missense mutations in the ACTA2 gene. Initially described as a case report in 1999, it was characterized in 2010 as a syndrome of congenital mydriasis, p ...
is a genetic condition in which the body of a developing embryo does not create enough smooth muscle for the gastrointestinal system. This condition is fatal. Anti-smooth muscle antibodies (ASMA) can be a symptom of an
auto-immune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
disorder, such as
hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...
,
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
, or lupus. Smooth muscle tumors are most commonly benign, and are then called leiomyomas. They can occur in any organ, but they usually occur in the
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
, small bowel, and
esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to t ...
. Malignant smooth muscle tumors are called
leiomyosarcoma Leiomyosarcoma is a malignant (cancerous) smooth muscle tumor. A benign tumor originating from the same tissue is termed leiomyoma. While leiomyosarcomas are not thought to arise from leiomyomas, some leiomyoma variants' classification is evolvi ...
s. Leiomyosarcomas are one of the more common types of soft-tissue sarcomas. Vascular smooth muscle tumors are very rare. They can be malignant or benign, and morbidity can be significant with either type.
Intravascular leiomyomatosis Intravenous leiomyomatosis is a rare condition seen exclusively in women in which leiomyomata, benign smooth muscle tumors, are found in veins. The masses are benign-appearing but can spread throughout the venous system leaving the uterus and ev ...
is a
benign neoplasm A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have rel ...
that extends through the
veins Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated ...
; angioleiomyoma is a benign neoplasm of the extremities; vascular leiomyosarcomas is a
malignant neoplasm Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
that can be found in the inferior vena cava, pulmonary arteries and
veins Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated ...
, and other
peripheral vessel The peripheral vascular system is the part of the circulatory system that consists of the veins and arteries not in the chest or abdomen (i.e. in the arms, hands, legs and feet). The peripheral arteries supply oxygenated blood to the body, an ...
s. See Atherosclerosis.


See also

*
Atromentin Atromentin is a natural chemical compound found in Agaricomycetes fungi in the orders Agaricales and Thelephorales. It can also be prepared by laboratory synthesis. Chemically, it is a polyphenol and a benzoquinone. Occurrences Atromentin has ...
has been shown to be a smooth muscle
stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
. * Myogenic mechanism


References


External links


BBC
– baby born with smooth muscle condition has 8 organs transplanted
Stomach smooth muscle identified using antibody
* * "Smooth Muscle" *
Smooth muscle histology photomicrographs
(medlineplus.gov) {{Authority control Muscular system Muscle tissue