Smooth muscle is a type of non-striated muscle, found within the "walls" of hollow organs and elsewhere like the bladder and abdominal cavity, the uterus, male and female reproductive tracts, the gastrointestinal tract, the respiratory tract, the vasculature, the skin and 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 and function.
The smooth muscle is spindle shaped , and like any muscle, can contract and relax. In relaxed state, each cell is spindle-shaped, 80-200 micrometers long and 5 micrometers wide. The cells that compose smooth muscle generally have single nuclei. The cells themselves are generally arranged in sheets or bundles and connected by gap junctions. In order to contract the cells contain intracellular contractile filamentous proteins called actin and myosin. While the filaments are essentially the same in smooth muscle as they are in skeletal and cardiac muscle, the way they are arranged is different (and some regulatory proteins are different). As non-striated muscle, the actin and myosin is not arranged into distinct sarcomeres that form orderly bands throughout the muscle cell. However there is an organized cytoskeleton and actin thin filaments attach to the sarcolemma by focal adhesions or attachment plaques. Some smooth muscle preparations can be visualized contracting in a spiral corkscrew fashion, and contractile proteins can organize into zones of actin and myosin along the axis of the cell. The sarcolemma possess microdomains specialized to cell signalling 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.
To a large extent, the arrangement of contractile elements in smooth muscle follows its function: to maintain organ dimensions against imposed loads. The thin and thick filament bundles are fastened to the sarcolemma (plasma membrane) of the cell via dense plaques or focal adhesions, and cells are fastened to one another via adherens junctions. Consequently, 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, facilitating the spread of chemicals (e.g., calcium) in single-unit smooth muscle.
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 may contract spontaneously or be induced by a number of physiochemical agents (e.g., hormones, drugs, neurotransmitters). 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 muscle type. For example, 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. It rhythmically massages products through the digestive tract as the result of phasic 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 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 it becomes 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 only work 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 the 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. In general, the relaxation of smooth muscle is by cell signalling pathways that increase the myosin phosphatase activity, decrease the intracellular calcium levels, and/or hyperpolarize the smooth muscle.
Smooth muscle can be characterized as two types: tonic and phasic which describes their response to 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, 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.
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, however there is a sustained maintenance of force in vascular smooth muscle. The sustained phase has been attributed to slowly cycling dephosphorylated myosin crossbridges and has been termed latch-bridges. 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 maintain the force at low energy costs. A number of kinases (Protein kinase C, ROCK kinase, Zip kinase) have been implicated as important cell signalling molecules during the sustained phase, and calcium flux may play a role.
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 is 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 regulate actin and focal adhesion dynamics, and recent evidence indicates that hsp20 binding to 14-3-3 protein is envolved in this process. 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.
In invertebrate smooth muscle, contraction is initiated with calcium directly binding to myosin and then rapidly cycling cross-bridges generating force. Similar to 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. Mollusk like clams use this catch phase of smooth muscle to keep their shell closed for prolonged periods with little energy usage.
Smooth muscle cells can be stimulated to contract or relax in many different ways. They may be directly stimulated by the autonomic nervous system ("involuntarily" control), but can also react on stimuli from neighbouring cells and on hormones (vasodilators or vasoconstrictor) within the medium that it carries.
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. There is a significant correlation between protein kinase G expression and a contractile smooth muscle phenotype. The cells are able to produce their own extracellular matrix. When cultured outside the body, the cells tend to differentiate into a synthetic phenotype, which is not able to contract.
The embryological origin of smooth muscle varies, but is usually of mesodermal origin. However, the Great Arteries of the heart are derived from ectomesenchyme of neural crest origin, although coronary artery smooth muscle is of mesodermal origin.
"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.
The content of this section is licensed under the GNU Free Documentation License (local copy). It uses material from the Wikipedia article "Smooth muscle" modified April 14, 2007 with previous authors listed in its history.