Smooth muscle



Smooth muscle is a type of non-striated muscle, found within the tunica media layer of arteries and veins, the bladder, uterus, male, female, and all animals, gastrointestinal tract, respiratory tract, 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, excitation-contraction coupling, and mechanism of contraction.

Structure
Smooth muscle fibers are spindle-shaped, and, like all muscle, can contract and relax. In the relaxed state, each cell is spindle-shaped, 20-500 micrometers long, and 5 micrometers wide. There are two types of smooth muscle arrangements in the body: multi-unit and single-unit. The single-unit type, also called unitary smooth muscle, is far more common. Whereas the former presents itself as distinct muscle fibers that are usually activated by their own nerve fibers, the latter operate as a single unit and are arranged in sheets or bundles. Unitary smooth muscle is also commonly referred to as visceral smooth muscle because it is found in the walls of the viscera, or internal organs, of the body, including the intestines, ducts such as the bile ducts, ureters and oviducts, and most blood vessels. Unitary smooth muscle can be further divided into phasic and tonic.

The cells that compose smooth muscle have, in general, single nuclei. The cells are arranged in sheets or bundles and connected by gap junctions. In order to contract, the cells contain actin filaments and a contractous protein called myosin. Whereas the filaments are essentially the same in smooth muscle as they are in skeletal and cardiac muscle, the way they are arranged is different. Some regulatory proteins also differ, and there are specific smooth muscle isoforms of actin and myosin. The smooth muscle cell contains less protein than a typical striated muscle cell and much less myosin. The actin content is similar, so the ratio of actin to myosin is ~6:1 in striated muscle and ~15:1 in smooth muscle. Smooth muscle does not contain the protein troponin, (calmodulin takes on the regulatory role in smooth muscle) and caldesmon and calponin are significant proteins expressed within smooth muscle. As non-striated muscle, the actin and myosin are not arranged into distinct sarcomeres that form orderly bands throughout the muscle cell. However, there is an organized cytoskeleton consisting of the intermediate filament proteins vimentin and desmin, along with actin filaments. Actin filaments attach to the sarcolemma by focal adhesions or attachment plaques and attach to other actin filaments via dense bodies (acting much like Z-lines in striated muscle). Evidence indicates that smooth muscle myosin is not bipolar with a central bare zone as in striated muscle, but is either side-polar or row-polar, and has no bare zone. 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-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.

Function
To maintain organ dimensions against forces, cells are fastened to one another 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. Smooth muscle may contract spontaneously (via ionic channel dynamic or Cajal pacemaker cells) or be induced by a number of physiochemical agents (e.g., hormones, drugs, neurotransmitters - particularly from the autonomic nervous system), and also mechanical stimulation (such as stretch).

Smooth muscles have been divided into "multi-unit" and "visceral" types or into "phasic" and "tonic" types based on the characteristics of the contractile patterns. 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. 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, rhythmically forcing foodstuffs through the digestive tract as the result of phasic contraction.

Smooth muscle in various regions of the vascular tree, the airway and lungs, kidneys, etc. is different in their expression of ionic channels, hormone receptors, cell-signaling pathways, and other proteins that determine function. 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.

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. Mollusk-like clams 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 ("involuntarily" control), but can also react on stimuli from neighbouring cells and on hormones (vasodilators or vasoconstrictor) within the medium that it carries.

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.