Smooth muscle

Smooth 'muscle' is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non-striated, so-called because it has no sarcomeres and therefore no striations. It can be divided into two subgroups, single-unit and multi-unit smooth muscle. Within single-unit muscle, the whole bundle or sheet of smooth muscle cells contracts as a syncytium.
Smooth muscle is found in the walls of hollow organs, including the stomach, intestines, bladder and uterus. In the walls of blood vessels, and lymph vessels, it is known as vascular smooth muscle. There is smooth muscle in the tracts of the respiratory, urinary, and reproductive systems. In the eyes, the ciliary muscles, iris dilator muscle, and iris sphincter muscle are types of smooth muscles. The iris dilator and sphincter muscles are contained in the iris and contract in order to dilate or constrict the pupils. The ciliary muscles change the shape of the lens to focus on objects in accommodation. In the skin, smooth muscle cells such as those of the arrector pili cause hair to stand erect in response to cold temperature and fear.

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 internal organs ; and lines blood vessels, the urinary tract, and the digestive tract. It is not found in the heart which has cardiac muscle.
In single-unit smooth muscle a single cell in a bundle is innervated by an autonomic nerve fiber. An action potential can be propagated through neighbouring muscle cells due to the presence of many gap junctions between the cells. Due to this property, single-unit bundles form a syncytium that contracts in a coordinated fashion making the whole muscle contract or relax, such as the uterine muscles during childbirth.
Single-unit visceral smooth muscle is myogenic; it can contract regularly without input from a motor 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, in the iris of the eye, and lining the large elastic arteries.
However, the terms single- and multi-unit smooth muscle represent an oversimplification. 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 and cardiac muscle in terms of structure, function, regulation of contraction, and excitation-contraction coupling. However, smooth muscle tissue tends 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. Smooth muscle in the gastrointestinal tract is activated by a composite of smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha that are electrically coupled and work together as an SIP functional syncytium.

Microanatomy

Smooth muscle cells

A smooth-muscle cell is a spindle-shaped myocyte with a wide middle and tapering ends, and a single nucleus. Like striated muscle, smooth muscle can tense and relax. In the relaxed state, each cell is 30–200 micrometers in length, some thousands of times shorter than a skeletal muscle cell. There are no myofibrils present, but much of the cytoplasm is taken up by the proteins, myosin and actin, which together have the capability to contract.

Myosin

Myosin is primarily class II in smooth muscle.

Myosin II contains two heavy chains which constitute the head and tail domains. Each of these heavy chains contains the N-terminal head domain, while the C-terminal tails take on a coiled-coil morphology, holding the two heavy chains together. Thus, myosin II has two heads. In smooth muscle, there is a single gene that codes for the heavy chains myosin II, but there are splice variants 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, resulting in 2 per head, weighing 20 and 17 kDa. 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. 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 is believed that it contributes to the structural stability of the myosin head along with MLC₂₀. Two variants of MLC₁₇ exist as a result of 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 contractions that are seen during the menstrual cycle.

Actin

The thin filaments that are part of the contractile machinery are predominantly composed of alpha-actin and gamma-actin. Smooth muscle alpha-actin is the predominant isoform within smooth muscle. There is also a lot of 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 to myosin is between 2:1 and 10:1 in smooth muscle. Conversely, from a mass ratio standpoint, 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; instead calmodulin, caldesmon and calponin are significant proteins expressed within smooth muscle.

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, tropomyosin serves to block actin–myosin interactions until calcium is present, but in smooth muscle, its function is unknown.
Calponin 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 activity of the myosin complex that otherwise provides energy to fuel muscle contraction.

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, and also attach intermediate filaments, and thereby appear to serve as anchors from which the thin filaments can exert force. 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. 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 in the cell membrane of the smooth muscle cell, called the sarcolemma. The adherens junctions consist of large number of proteins including alpha-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 areas alternate with regions of membrane containing numerous caveolae. 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 Ser⁵⁶ 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 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, elastin, glycoproteins, and proteoglycans. 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 of these tissues. For example, the great arteries are viscolelastic vessels that act like a Windkessel, propagating ventricular contraction and smoothing out the pulsatile flow, and the smooth muscle within the tunica media contributes to this property.