Smooth muscle
1. Mucosa
2. Submucosa
3. Muscularis
4. Adventitia
5. Striated muscle
6. Striated and smooth
7. Smooth muscle
8. Lamina muscularis mucosae
9. Esophageal glands
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit (unitary) and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by gap junctions to neighboring cells such that the whole bundle or sheet contracts as a syncytium (i.e., a multinucleate mass of cytoplasm that is not separated into cells). Multiunit smooth muscle tissues innervate individual cells; as such, they allow for fine control and gradual responses, much like motor unit recruitment in skeletal muscle.
Most smooth muscle is of the single-unit variety, but there is multiunit smooth muscle in the trachea, the large elastic arteries, and the iris of the eye. There is a remarkable diversity of these smooth muscle types. Smooth muscle is found in many places; within the tunica media layer of large (aorta) and small arteries, veins,and lymphatic vessels, the urinary bladder, uterus, male and female reproductive tracts, gastrointestinal tract, respiratory tract, arrector pili of skin, the ciliary muscle, and iris of the eye. The glomeruli of the kidneys contain a smooth muscle-like cell called the mesangial cell. Smooth muscle is fundamentally different from skeletal muscle and cardiac muscle in terms of structure, function, regulation of contraction, and excitation-contraction coupling.
Smooth muscle fibers have a fusiform shape and, like striated muscle, can tense and relax. However smooth muscle containing tissue tend 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. In the relaxed state, each cell is spindle-shaped, 20-500 micrometers in length. The ratio of actin to myosin is ~6:1 in skeletal muscle, 4:1 in cardiac muscle and ~16.5:1 in smooth muscle. 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 is present in smooth but doesn't serve the same regulatory function as in striated muscle. The major protein components of smooth muscle thin filaments are actin, tropomyosin and caldesmon. These proteins are present in the molar ratios of 28:4:1 respectively. Smooth muscle cells possess abundant adherens junctions that anchor actin filaments and intermediate filaments which also interact with dense bodies. Dense bodies and adherens junctions are rich in the protein actinin which is also a predominate Z-line protein in striated muscle. There is an organized cytoskeleton consisting of the intermediate filament proteins vimentin and desmin, along with actin filament that interact with adherens junctions (also called focal adhesions) in the sarolemma and dense bodies in the cytoplasm such when actin and myosin interact force is transduced to the sarcolemma. Smooth muscle cells have been observed contracting in a spiral corkscrew fashion, and contractile proteins have been observed organizing into zones of actin and myosin along the axis of the cell.
The sarcolemma possess microdomains specialized to cell-signaling events and ion channels called caveolae. These invaginations in the sarcoplasma 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, ATP sensitive Potassium channels, Calcium sensitive Potassium channels) in close proximity. The caveolae are often in close proximity to sarcoplasmic reticulum or mitochondria, and have been proposed to organize signaling molecules in the membrane.
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Function
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. Smooth muscle may contract spontaneously (via ionic channel dynamics) or as in the gut special pacemakers cells interstitial cells of Cajal produce rhythmic contractions. Contraction and relaxation can be induced by a number of physiochemical agents (e.g., hormones, drugs, neurotransmitters - particularly from the autonomic nervous system. Single unit smooth muscle is most common and lines blood vessels (except large elastic arteries), the urinary tract, and the digestive tract. Smooth muscle forms precapillary sphincters which regulates the blood flow in capillary beds of various organs and tissues. Smooth muscle often tends to contract rhythmically, is coupled by numerous gap junctions, and often exhibits spontaneous action potentials. Another nomenclature separates smooth muscle by contractile pattern. It 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. The contractile function of vascular smooth muscle is critical to regulating the lumenal diameter of the small arteries-arterioles called resistance vessels. The resistance arteries contribute significantly to setting the level of blood pressure. Smooth muscle contracts slowly and may maintain the contraction (tonically) for prolonged periods in blood vessels, bronchioles, and some sphincters. 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. 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.
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. 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. Specialized smooth muscle within the afferent arteriole of the juxtaglomerular apparatus secretes renin in response to osmotic and pressure changes, and also it is believed to secrete ATP in tubuloglmerular regulation of glomerular filtration rate. Renin in turn activates the angiotensin system to regulate blood pressure. Smooth muscle-containing tissue often must be stretched, 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, glycoproteins, and proteoglycans. These fibers with their extracellular matrices contribute to the viscoelasticity of these tissues. Smooth muscle also has specific elastin and collagen receptors to interact with these proteins.
Contraction and relaxation basics
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 adopt their original conformation. They can then re-bind to another part of 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 cannot occur until the myosin heads have been activated to allow crossbridges to form. The myosin heads are made up of heavy chains and light protein chains. 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). 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. The phosphorylation of the light chains by MLCK is countered by a myosin light-chain phosphatase, which dephosphorylates the myosin light chains and inhibits the 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 dynamics.
Phosphorylation of the 20 kd 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, 20 kd myosin light chains phosphorylation decreases, and energy utilization decreases and the muscle can relax, however there is a sustained maintenance of force in vascular smooth muscle. The sustained phase has been attributed to slowly cycling dephosphorylated myosin crossbridges termed latch-bridges and actin polymerization stiffening the cell. During contraction of muscle, rapidly cycling crossbridges form between activated actin and phosphorylated myosin generating force. During the sustained phase, phosphorylation levels decline and slow cycling dephosphorylated crossbridges act as latch bridges to contribute to maintaining the force at low energy costs. 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. 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 form interacting with actin.
Advances and current research in contraction and relaxation
Muscle can be characterized as two types: tonic and phasic which describes their response too depolarizing high potassium solutions. Tonic smooth muscle contracts and relaxes slowly and exhibits force maintenance such as vascular smooth muscle. Force maintenance is the maintaining of a contraction for a prolonged time with little energy utilization. The phasic smooth muscle contracts and relaxes rapidly such as gut smooth muscle. This phasic response is useful to massage substances through the lumen of the gastrointestinal tract during peristalsis. Vascular smooth muscle (walls of arteries and veins) and visceral smooth muscle (wall of gastrointestinal tract, it is found on the penis, urogenital tract, iris) is another distinction in common use to discriminate the kind of smooth muscle. Contractions in vertebrate smooth muscle can be initiated by stretch, gap junction electrical, and neural and humoral receptor mediated agents (acetylcholine, endothelin, etc.). Smooth muscle in the gastrointestinal and urogenital tracts is regulated by the enteric nervous system and by peristaltic pacemaker cells—the interstitial cells of Cajal.
Stretch, neural and humoral agents, and gap junction activity that depolarize the sarcolemma increase intracellular calcium. Extracellular calcium enters through L type calcium channels and intracellular calcium is released from stored calcium in the sarcoplasmic reticulum. Calcium release from the sarcoplasmic reticulum is through Ryanodine receptor channels (calcium sparks) by a redox process and inositol triphosphate receptor channels by the second messenger inositol triphosphate. The intracellular calcium binds with calmodulin which then binds and activates myosin-light chain kinase. The calcium-calmodulin-myosin light chain kinase complex phosphorylates the 20 kilodalton (kd) myosin light chains on amino acid residue-serine 19 to initiate contraction. The phosphorylation of the myosin light chains then allows the myosin ATPase to function. The thin filament associated proteins caldesmon and calponin are also believed to serve a function in contractility within smooth muscle. During contraction actin polymerization also occurs and it appears to be significant in the process.
Phosphorylation of the 20 kd 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, 20 kd myosin light chains phosphorylation decreases, and energy utilization decreases and the muscle can relax, however there is a sustained maintenance of force in vascular smooth muscle. The sustained phase has been attributed to slowly cycling dephosphorylated myosin crossbridges termed latch-bridges and actin polymerization stiffening the cell. During contraction of muscle, rapidly cycling crossbridges form between activated actin and phosphorylated myosin generating force. During the sustained phase, phosphorylation levels decline and slow cycling dephosphorylated crossbridges act as latch bridges to contribute to maintaining the force at low energy costs. Other cell signalling pathways and protein kinases (Protein kinase C, ROCK kinase, Zip kinase, Focal adhesion kinases) have been implcated and actin polymerization dynamics plays a role in force maintenance. While myosin light chain phosphorylation correlates well with shortening velocity, other cell signalling 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.
Phosphorylation of the 20kd myosin light chains is counteracted by a myosin light chain phosphatase that dephosphorylates the myosin light chains. 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.
The relaxation of smooth 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. These cyclic nucleotides activate Protein Kinase G and Proten Kinase A and phosphorylate a number of proteins. The phosphorylation events lead to a decrease in intracelluar calcium (inhibit L type Calcium channels, inhibits IP3 receptor 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. 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.
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.[1]
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.
Control
Smooth muscle cells can be stimulated to contract or relax in many different ways. They may be directly stimulated by the autonomic nervous system (involuntary control), but can also react on stimuli from neighbouring cells and on hormones (vasodilators or vasoconstrictor) within the medium that it carries. Specialized smooth muscle cells within the afferent arteriole of the juxtaglomerular apparatus of kidney produces renin which activates the angiotension II system.
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 embryological origin of smooth muscle is usually of mesodermal origin. 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
"Smooth muscle condition" is a 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 disorder, such as hepatitis, cirrhosis, or lupus.
Vascular smooth muscle tumors are very rare. They can be 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 malign neoplasm that can be found in the inferior vena cava, pulmonary arteries and veins, and other peripheral vessels.
See Atherosclerosis.
See Asthma.
See also
References
- ↑ Scherer EQ et al. Sphingosine-1-phosphate modulates spiral modiolar artery tone: A potential role in vascular-based inner ear pathologies? Cardiovasc Res. 2006 Apr 1;70(1):79–87.
External links
- BBC - baby born with smooth muscle condition has 8 organs transplanted
- Smooth muscle antibody
- Stomach smooth muscle identified using antibody
- UIUC Histology Subject 265
- Histology at KUMC muscular-muscle08 "Smooth Muscle"
- Histology at BU 21701ooa
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