Smooth muscle
Smooth muscle | |
---|---|
veins | |
Details | |
Identifiers | |
Latin | muscularis levis; muscularis nonstriatus |
MeSH | D009130 |
TH | H2.00.05.1.00001 |
FMA | 14070 |
Anatomical terminology] |
Smooth(soft) muscle is an involuntary non-
Smooth muscle is found in the walls of
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
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 is not receiving any neural stimulation. Multiunit smooth muscle is found in the trachea, the iris of the eye, and lining the large elastic arteries.
However, the terms single- and multi-unit smooth muscle represents an
Smooth muscle differs from
Microanatomy
Smooth muscle cells
A smooth muscle cell is a spindle-shaped
Myosin
Myosin is primarily class II in smooth muscle.[8]
- MYH11[9]) that codes for the heavy chains myosin II, but there are splice variants of this gene that result in four distinct isoforms.[8] Also, smooth muscle may contain MHC that is not involved in contraction, and that can arise from multiple genes.[8]
- Myosin II also contains 4 light chains (MLC), resulting in 2 per head, weighing 20 (MLC20) and 17 (MLC17) kDa.[8]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.[8] 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.[8] Its exact function is unclear, but it is believed that it contributes to the structural stability of the myosin head along with MLC20.[8] Two variants of MLC17 (MLC17a/b) exist as a result of alternative splicing at the MLC17 gene.[8]
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.
Actin
The thin filaments that are part of the contractile machinery are predominantly composed of alpha-actin and gamma-actin.[8] 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.[8] Alpha-actin is also expressed as distinct genetic isoforms such as smooth muscle, cardiac muscle and skeletal muscle specific isoforms of alpha-actin.[10]
The ratio of actin to myosin is between 2:1[8] and 10:1[8] 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.[11][12][13][14]
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.
- striated muscle, tropomyosin serves to block actin–myosin interactions until calcium is present, but in smooth muscle, its function is unknown.[8]
- Calponin molecules may exist in equal number as actin, and has been proposed to be a load-bearing protein.[8]
- Caldesmon has been suggested to be involved in tethering actin, myosin and tropomyosin, and thereby enhance the ability of smooth muscle to maintain tension.[8]
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.[8]
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),[8] 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.[8] 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.[8] Dense bodies appear darker under an electron microscope, and so they are sometimes described as electron dense.[15]
The intermediate filaments are connected to other intermediate filaments via dense bodies, which eventually are attached to
Contraction
During contraction, there is a spatial reorganization of the contractile machinery to optimize force development.
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
Caveolae
The sarcolemma also contains
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
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
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.[citation needed]
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 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 tone.[16]
Spread of impulse
To maintain organ dimensions against force, cells are fastened to one another by
Contraction
Smooth muscle contraction is caused by the sliding of myosin and actin filaments (a sliding filament mechanism) over each other. The energy for this to happen is provided by the hydrolysis 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). 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.[8] 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.[1]
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,[8] 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.[8] Phosphorylation of a threonine on position 18 (Thr18) on MLC20 is also possible and may further increase the ATPase activity of the myosin complex.[8]
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.[8] This phenomenon is of great value especially for tonically active smooth muscle.[8]
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 (
Relaxation
The phosphorylation of the light chains by MLCK is countered by a
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
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
See also
- Atromentin has been shown to be a smooth muscle stimulant.[17]
- Myogenic mechanism
- List of distinct cell types in the adult human body
References
- ^ a b c d Betts, J. Gordon; Young, Kelly A.; Wise, James A.; Johnson, Eddie; Poe, Brandon; Kruse, Dean H.; Korol, Oksana; Johnson, Jody E.; Womble, Mark; Desaix, Peter (6 March 2013). "Smooth muscle". Archived from the original on 7 October 2021. Retrieved 10 June 2021.
- ^ "Thesaurus results for Striated". www.merriam-webster.com. Retrieved 22 April 2022.
- ^ "10.8 Smooth Muscle - Anatomy and Physiology | OpenStax". openstax.org. 25 April 2013. Retrieved 10 May 2022.
- ^ Berne & Levy. Physiology, 6th Edition
- PMID 27778026.
- PMID 24987007.
- ^
- ^ PMID 20551073.
- PMID 7684189.
- PMID 20737541.
- ^ Aguilar_2010 (above reference) "In skeletal or striated muscle, there is 3-fold more myosin than actin."
- ^ Trappe S, Gallagher P, et al. Single muscle fibre contractile properties in young and old men and women. J Physiol (2003), 552.1, pp. 47–58, Table 8
- ^ Greger R, Windhorst U; Comprehensive Human Physiology, Vol. II. Berlin, Springer, 1996; Chapter 46, Table 46.1, Myosin 45%, Actin 22% of skeletal muscle myofibrillar proteins, p. 937
- ^ Lawrie's Meat Science, Lawrie RA, Ledward, D; 2014; Chapter 4, Table 4.1, Chemical Composition of Typical Mammalian Adult Muscle, percent of skeletal muscle tissue wet weight; myosin 5.5%, actin 2.5%, p. 76
- )
- PMID 16533504.
- PMID 5815216.
External links
- BBC – baby born with smooth muscle condition has 8 organs transplanted
- Smooth muscle antibody Archived 2009-03-16 at the Wayback Machine
- Stomach smooth muscle identified using antibody Archived 2015-09-23 at the Wayback Machine
- UIUC Histology Subject 265
- Histology at KUMC muscular-muscle08 "Smooth Muscle"
- Histology image: 21701ooa – Histology Learning System at Boston University
- Smooth muscle histology photomicrographs
- Where smooth muscle tissue is found in the body (medlineplus.gov)