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Smooth muscle is an involuntary non-
striated muscle 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 obser ...

striated muscle
, so-called because it has no
sarcomere A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue Striated muscle tissue is a muscle tissue Muscle tissue is a soft tissue that composes muscles in animal bodie ...

sarcomere
s and therefore no
striations Striations means a series of ridges, furrows or linear marks, and is used in several ways: * Glacial striation * Striation (fatigue), in material * Striation (geology), a ''striation'' as a result of a geological Fault (geology), fault * Striation ...

striations
. 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 A contract is a legally binding document between at least two parties that defines and governs the rights and duties of the parties to an agreement. A contract is legally enforceable because it meets the requirements and approval of the law. A ...

contracts
as a
syncytium A syncytium or symplasm (; plural syncytia; from Greek: σύν ''syn'' "together" and κύτος ''kytos'' "box, i.e. cell") is a multinucleate cell which can result from multiple cell fusions of uninuclear cells (i.e., cells with a single nucleu ...

syncytium
. Smooth muscle is found in the walls of
hollow organ An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly categorized as parenchyma, the tissue peculiar to (or at least arch ...
s, including the
stomach The stomach is a muscular, in the of humans and many other animals, including several s. The stomach has a dilated structure and functions as a vital organ. In the digestive system the stomach is involved in the second phase of digestion, ...

stomach
,
intestines The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syst ...
,
bladder The urinary bladder, or simply bladder, is a hollow muscular organ in humans and other vertebrates that stores urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ure ...
and
uterus The uterus (from Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken in the area around Rome, known as Latium. Through the power of the ...

uterus
; in the walls of passageways, such as
blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible In fluid mechanics or more generally continuum mechanics, incompressible flow (isochoric process, isochoric flow) refers t ...
, and
lymph vessel The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes) structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessels a ...

lymph vessel
s, and in the tracts of the
respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system A biological system is a complex biological network, network which connects several biologically relevant entities. Biological organization spans sever ...
,
urinary The urinary system, also known as the renal system or urinary tract, consists of the kidneys, ureters, bladder The urinary bladder, or simply bladder, is a hollow muscular organ in humans and other vertebrates that stores urine Urine is ...
, and
reproductive Reproduction (or procreation or breeding) is the biological process by which new individual organisms – "offspring" – are produced from their "parent" or parents. Reproduction is a fundamental feature of all known life; each individual orga ...
systems. In the
eyes Eyes are organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly categorized as parenchyma Parenchyma () is th ...

eyes
, the
ciliary muscle The ciliary muscle is a ring of smooth muscleSchachar, Ronald A. (2012). "Anatomy and Physiology." (Chapter 4) . in the eye's middle layer ( vascular layer) that controls accommodation for viewing objects at varying distances and regulates the ...
, a type of smooth muscle, dilate and contract the iris and alter the shape of the
lens A lens is a transmissive optical Optics is the branch of physics Physics is the natural science that studies matter, its Elementary particle, fundamental constituents, its Motion (physics), motion and behavior through Spacetime, s ...
. 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 cuticle, animal coverings, such as the arthropod exoskeleton, have differ ...

skin
, smooth muscle cells such as those of the
arrector pili The arrector pili muscles, also knows as hair erector muscles, are small muscles attached to hair follicles The hair follicle is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with si ...
cause
hair Hair is a protein filament In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Ph ...

hair
to stand erect in response to
cold , a common physiological response to cold, aiming to reduce the loss of body heat in a cold environment File:AntarcticaDomeCSnow.jpg, A photograph of the snow surface at Dome C Station, Antarctica a part of the notoriously cold Polar Platea ...

cold
temperature or
fear Fear is an intensely unpleasant emotion Emotions are mental state, psychological states brought on by neurophysiology, neurophysiological changes, variously associated with thoughts, feelings, behavioural responses, and a degree of pleasure ...

fear
.


Structure


Gross anatomy

Most smooth muscle is of the single-unit variety, that is, either the whole muscle contracts or the whole muscle relaxes, but there is multiunit smooth muscle in the
trachea The trachea, also known as the windpipe, is a tube that connects the to the bronchi of the s, allowing the passage of , and so is present in almost all air- s with lungs. The trachea extends from the larynx and branches into the two primary . ...

trachea
, the large elastic arteries, and the iris of the eye. Single unit smooth muscle, however, is most common and lines blood vessels (except large elastic arteries), the
urinary tract The urinary system, also known as the renal system or urinary tract, consists of the kidneys, ureters, bladder The urinary bladder, or simply bladder, is a hollow muscular organ in humans and other vertebrates that stores urine Urine is ...
, and the
digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syst ...
. However, the terms single- and multi-unit smooth muscle represents an
oversimplification The fallacy of the single cause, also known as complex cause, causal oversimplification, causal reductionism, and reduction fallacy, is an informal fallacy Informal fallacies are a type of incorrect argument In logic Logic (from Ancient Gre ...
. 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 Organ (biology), organs of the vertebrate muscular system that are mostly attached by tendons to bones of the skeleton. The muscle cells of skeletal muscles are much longer than in the other ...

skeletal muscle
and
cardiac muscle Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biol ...

cardiac muscle
in terms of structure, function, regulation of contraction, and
excitation-contraction coupling Muscle contraction is the activation of tension Tension may refer to: Science * Psychological stress * Tension (physics), a force related to the stretching of an object (the opposite of compression) * Tension (geology), a stress which stretches r ...
. However, smooth muscle tissue tends to demonstrate greater elasticity and function within a larger length-tension curve than
striated muscle 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 obser ...

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 The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system The human digestive system consists of the gastrointestinal tract The gastrointestinal tract, (GI tract, GIT, d ...
is activated by a composite of three types of cells –
smooth muscle cells Smooth muscle is an involuntary non-striated muscle 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, w ...
(SMCs),
interstitial cells of Cajal The interstitial cell of Cajal (ICC) is a type of interstitial cell found in the gastrointestinal tract The gastrointestinal tract, (GI tract, GIT, digestive tract, digestion tract, alimentary canal) is the tract from the mouth to the anu ...
(ICCs), and platelet-derived growth factor receptor alpha (PDGFRα) that are electrically coupled and work together as an .


Microanatomy


Smooth muscle cells

Smooth muscle cells known as
myocyte A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell Cardiac muscle cells or cardiomyocytes (also known as myocardiocytes or cardiac myocytes) are the muscle cells (myocyte A myocyte is a muscle cell of the ...
s, are spindle-shaped with a wide middle and tapering ends, and like striated muscle, can . In the relaxed state, each cell is 30–200 micrometers in length. There are no
myofibril s in parallel, and sarcomere A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the complicated unit of striated muscle tissue. It is the repeating unit between two Z lines. Skeletal muscles are composed of tubular mu ...

myofibril
s present but much of the cytoplasm is taken up by the proteins of
myosin Myosins () are a superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilie ...

myosin
and
actin Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments. It is found in essentially all Eukaryote, eukaryotic cells, where it may be present at a concentration of over 100 Micromolar, μ ...
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 Myosins () are a superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilie ...
contains two ''heavy chains'' (MHC) which constitute the head and tail domains. Each of these heavy chains contains the
N-terminal 350px, A Val-Glycine.html"_;"title="Valine.html"_;"title="tetrapeptide_(example:_Valine">Val-Glycine">Gly-Serine">Ser-Alanine.html" ;"title="Glycine">Gly-Serine.html" ;"title="Valine">Val-Glycine.html" ;"title="Valine.html" ;"title="tetrapeptid ...

N-terminal
head domain, while the
C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid Amino acids are organic compound , CH4; is among the simplest organic compounds. In chemistr ...

C-terminal
tails take on a
coiled-coil A coiled coil is a structural motif In a polymer, chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated ...
morphology, holding the two heavy chains together (imagine two snakes wrapped around each other, such as in a
caduceus The caduceus (☤; ; la, cādūceus, from grc-gre, κηρύκειον "herald's wand, or staff") is the staff carried by Hermes in Greek mythology and consequently by Hermes Trismegistus in Greco-Egyptian mythology. The same staff was also b ...

caduceus
). Thus, myosin II has two heads. In smooth muscle, there is a single gene (
MYH11 Myosin-11 is a protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme cataly ...
) that codes for the heavy chains myosin II, but there are 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 The dalton or unified atomic mass unit (symbols: Da or u) is a unit Unit may refer to: Arts and entertainment * UNIT, a fictional military organization in the science fiction television series ''Doctor Who'' * Unit of action, a discrete piece of ...
. 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 Tension may refer to: Science * Psychological stress * Tension (physics), a force related to the stretching of an object (the opposite of compression) * Tension (geology), a stress which stretches ...

muscle contraction
. 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 Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression Gene expression is the process by which information from a gene In biology, a gene (from ''genos'' ". ...

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 contractionsA uterine contraction is a muscle contraction of the uterine smooth muscle. Throughout menstrual cycle The uterus frequently contracts throughout the entire menstrual cycle, and these contractions have been termed ''endometrial waves'' or ''contr ...
that are seen during the menstrual cycle.


Actin

The thin filaments that are part of the contractile machinery are predominantly composed of α- and γ-actin. Smooth muscle α-actin (alpha actin) is the predominant isoform within smooth muscle. There is also a lot of actin (mainly β-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 protein family, family of Globular protein, globular multi-functional proteins that form microfilaments. It is found in essentially all Eukaryote, eukaryotic cells, where it may be present at a concentration of over 100 Micromolar, μ ...
to
myosin Myosins () are a superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilie ...

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 image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL Troponin, or ...
; instead
calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells Eukaryotes () are organism In biology Biology is the na ...

calmodulin
(which takes on the regulatory role in smooth muscle), caldesmon and are significant proteins expressed within smooth muscle. *
Tropomyosin Tropomyosin is a two-stranded alpha-helical, coiled coil protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of ...

Tropomyosin
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 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 obser ...

striated muscle
, tropomyosin serves to block actin–myosin interactions until calcium is present, but in smooth muscle, its function is unknown. * 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 ATPases (, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, adenosine 5'-triphosphatase, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
activity of the myosin complex that otherwise provides energy to fuel muscle contraction.


Dense bodies

The actin filaments are attached to dense bodies. Dense bodies are rich in α-actinin, and also attach
intermediate filament Intermediate filaments (IFs) are cytoskeletal 300px, The eukaryotic cytoskeleton. Actin filaments are shown in red, and microtubules composed of beta tubulin are in green. The cytoskeleton is a complex, dynamic network of interlinking prote ...

intermediate filament
s (consisting largely of
vimentin Vimentin is a structural protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, incl ...

vimentin
and
desmin Desmin is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for whi ...
), and thereby appear to serve as anchors from which the thin filaments can exert force. Dense bodies also are associated with β-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 Adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions in epithelial and endothelial tissues, usually more basal than tight junctions Tight junctions, also kn ...
(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 A biological membrane, biomembrane or cell membrane is a selectively permeable membra ...

cell membrane
of the smooth muscle cell, called the
sarcolemma The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath) also called the myolemma, is the cell membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasm ...
. The adherens junctions consist of large number of proteins including 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 In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, D ...
. 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 56 by a p21 activated kinase, 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 Collagen () is the main structural protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowder ...

collagen
(predominantly types I and III),
elastin Elastin is a key protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, f ...
,
glycoproteins Glycoproteins are protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including ...
, and
proteoglycans Proteoglycans are protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958 ...
. 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 In materials science The interdisciplinary Interdisciplinarity or interdisciplinary studies involves the combination of two or more academic disciplines into one activity (e.g., a research project). It draws knowledge from several other ...
of these tissues. For example, the great arteries are viscolelastic vessels that act like a , 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 (biology), 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 mad ...
contributes to this property.


Caveolae

The sarcolemma also contains
caveolae In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, D ...
, which are microdomains of
lipid raft The plasma membranes of cells contain combinations of glycosphingolipidImage:Sphingosine structure.svg, Sphingosine Glycosphingolipids are a subtype of glycolipids containing the amino alcohol sphingosine. They may be considered as sphingolipids w ...
s specialized to
cell signaling In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms ...
events and
ion channels s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. Ion channels are pore-forming membrane protein Membrane proteins are common proteins ...

ion channels
. These invaginations in the sarcoplasm contain a host of
receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ne ...

receptors
(
prostacyclin Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin The prostaglandins (PG) are a group of physiologically active lipid In biology Biology is the natural science that studies life and living organisms, including thei ...

prostacyclin
,
endothelin Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute to ...
,
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter Monoamine neurotransmitters are s and s that contain one group connected to an by a two-carbon chain (such as -CH2-CH2-). Examples are , and . All monoamines are ...

serotonin
,
muscarinic receptors - the natural agonist of muscarinic and nicotinic receptors. - an agonist used to distinguish between these two classes of receptors. Not normally found in the body. Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors t ...
,
adrenergic receptor (yellow) on its extracellular site. β2 stimulates cells to increase energy production and utilization. The membrane the receptor is bound to in cells is shown with a gray stripe.The adrenergic receptors or adrenoceptors are a class of G protein- ...
s),
second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intracellular signals, a non-local form or cell signaling In biology Biology is ...
generators (,
phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , ...
),
G proteins G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell Cell most often refers to: ...
(RhoA, G alpha), kinases (
rho kinase Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of Serine/threonine-specific protein kinase, serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells ...
-ROCK,
protein kinase C In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and th ...
,
protein Kinase A In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, ...
), 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 exp ...
, ATP sensitive potassium channels, calcium sensitive
potassium channels are indicated by red and blue lines.Potassium channels are the most widely distributed type of ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 ...
) 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 dynamics) or as in the gut special pacemakers cells
interstitial cells of Cajal The interstitial cell of Cajal (ICC) is a type of interstitial cell found in the gastrointestinal tract The gastrointestinal tract, (GI tract, GIT, digestive tract, digestion tract, alimentary canal) is the tract from the mouth to the anu ...
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 The autonomic nervous system (ANS), formerly the vegetative nervous system, is a division of the peripheral nervous system that supplies smooth muscle and glands, and thus influences the function of viscera, internal organs. The autonomic nervous ...

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 , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and ...

norepinephrine
and
epinephrine Adrenaline, also known as epinephrine, is a hormone A hormone (from the Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a co ...

epinephrine
(from sympathetic stimulation or the adrenal medulla) by producing vasoconstriction (this response is mediated through
alpha-1 adrenergic receptors The alpha-1 (α1) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gq alpha subunit, Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-adrenergic, α1A-, α1B-adrenergic, α1B ...
). However, blood vessels within skeletal muscle and cardiac muscle respond to these
catecholamines (noradrenaline) Image:Adrenalin - Adrenaline.svg">140px, epinephrine (adrenaline) A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol">organic_compound.html" ;"title="monoamine neurotra ...
producing vasodilation because they possess beta-
adrenergic receptors (yellow) on its extracellular site. β2 stimulates cells to increase energy production and utilization. The membrane the receptor is bound to in cells is shown with a gray stripe.The adrenergic receptors or adrenoceptors are a class of G protein- ...
. 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 Sphingosine-1-phosphate (S1P) is a signaling In signal processing Signal processing is an electrical engineering subfield that focuses on analysing, modifying, and synthesizing signals such as audio signal processing, sound, image proc ...

sphingosine-1-phosphate
(S1P) signaling is an important regulator of
vascular smooth muscle Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels. Structure Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood ...
contraction. When transmural pressure increases,
sphingosine kinase 1 Sphingosine kinase 1 is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the ...
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 myosin light-chain kinase, 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 tone.


Spread of impulse

To maintain organ dimensions against force, cells are fastened to one another by
adherens junctions Adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions in epithelial and endothelial tissues, usually more basal than tight junctions Tight junctions, also kn ...
. 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 Myosins () are a superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilie ...

myosin
and
actin Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments. It is found in essentially all Eukaryote, eukaryotic cells, where it may be present at a concentration of over 100 Micromolar, μ ...
filaments (a Sliding filament theory, sliding filament mechanism) over each other. The energy for this to happen is provided by the hydrolysis of Adenosine triphosphate, 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 Tension may refer to: Science * Psychological stress * Tension (physics), a force related to the stretching of an object (the opposite of compression) * Tension (geology), a stress which stretches ...

muscle contraction
). 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 (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 Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells Eukaryotes () are organism In biology Biology is the na ...

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 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 Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin The prostaglandins (PG) are a group of physiologically active lipid In biology Biology is the natural science that studies life and living organisms, including thei ...

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 channels, stimulates SERCA, 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 artery, 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 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 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 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 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 antibody, Anti-smooth muscle antibodies (ASMA) can be a symptom of an auto-immune disorder, such as hepatitis, cirrhosis, or Lupus erythematosus, lupus. Smooth muscle tumour, Smooth muscle tumors are most commonly benign, and are then called leiomyomas. They can occur in any organ, but the usually occur in the
uterus The uterus (from Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken in the area around Rome, known as Latium. Through the power of the ...

uterus
, small bowel, and esophagus. Malignant smooth muscle tumors are called leiomyosarcomas. Leiomyosarcomas are one of the more common types of soft-tissue sarcomas. Vascular smooth muscle tumors are very rare. They can be Neoplasm#Types, malignant or benign, and morbidity can be significant with either type. Intravascular leiomyomatosis is a benign neoplasm that extends through the veins; angioleiomyoma is a benign neoplasm of the extremities; vascular leiomyosarcomas is a malignant neoplasm that can be found in the inferior vena cava, pulmonary arteries and pulmonary veins, veins, and other peripheral vessels. See Atherosclerosis.


See also

* Atromentin has been shown to be a smooth muscle stimulant. * Skeletal muscle * Cardiac muscle


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