101 Sentences With "sarcolemma" | Random Sentence Generator

The soreness is associated with temporary damage to muscle contractile proteins and/or the muscle sarcolemma.

Dr. Mendell presented the following preliminary data on the first three patients enrolled in the study: *All patients showed robust expression of transduced micro-dystrophin, which is properly localized to the muscle sarcolemma, as measured by immunohistochemistry.

Detailed view of a neuromuscular junction: 1\. Presynaptic terminal 2\. Sarcolemma 3\. Synaptic vesicle 4\.

Myofibril Detailed view of a neuromuscular junction: 1\. Presynaptic terminal 2\. Sarcolemma 3\. Synaptic vesicle 4\.

Dystrophin is a protein located between the sarcolemma and the outermost layer of myofilaments in the muscle fiber (myofiber). It is a cohesive protein, linking actin filaments to other support proteins that reside on the inside surface of each muscle fiber's plasma membrane (sarcolemma). These support proteins on the inside surface of the sarcolemma in turn links to two other consecutive proteins for a total of three linking proteins. The final linking protein is attached to the fibrous endomysium of the entire muscle fiber.

This is mostly the result of abnormal function of the dystrophin-glycoprotein-associated complex in the sarcolemma of skeletal muscles.

Myotonia may present in the following diseases with different causes related to the ion channels in the skeletal muscle fiber membrane (sarcolemma).

At the neuromuscular junction presynaptic motor axons terminate 30 nanometers from the cell membrane or sarcolemma of a muscle fiber. The sarcolemma at the junction has invaginations called postjunctional folds, which increase its surface area facing the synaptic cleft. These postjunctional folds form the motor endplate, which is studded with nicotinic acetylcholine receptors (nAChRs) at a density of 10,000 receptors/micrometer2. The presynaptic axons terminate in bulges called terminal boutons (or presynaptic terminals) that project toward the postjunctional folds of the sarcolemma. In the frog each motor nerve terminal contains about 300,000 vesicles, with an average diameter of 0.05 micrometers.

T-tubules are tubules formed from the same phospholipid bilayer as the surface membrane or sarcolemma of skeletal or cardiac muscle cells. They connect directly with the sarcolemma at one end before travelling deep within the cell, forming a network of tubules with sections running both perpendicular (transverse) to and parallel (axially) to the sarcolemma. Due to this complex orientation, some refer to T-tubules as the transverse-axial tubular system. The inside or lumen of the T-tubule is open at the cell surface, meaning that the T-tubule is filled with fluid containing the same constituents as the solution that surrounds the cell (the extracellular fluid).

The newborn larvae migrate from the host's blood vessels through the sarcolemma of striated muscle tissue, where they penetrate and encyst inside an individual muscle cell.

With a singular neuromuscular junction, each muscle fiber receives input from just one somatic efferent neuron. Action potential in a somatic efferent neuron causes the release of the neurotransmitter acetylcholine. When the acetylcholine is released it diffuses across the synapse and binds to a receptor on the sarcolemma, a term unique to muscle cells that refers to the cell membrane. This initiates an impulse that travels across the sarcolemma.

Costameres have several primary functions. First, they keep the sarcolemma in line with the sarcomere during contraction and subsequent relaxation. They are also responsible for the lateral transmission of the sarcomere-generated contractile force to the sarcolemma and the ECM. Only 20-30% of the total force generated by sarcomere contraction is transmitted longitudinally, suggesting that the majority of the force generated by sarcomeres is transduced in the lateral direction, perpendicular to the contracting myofibril fibers.

Muscle cells are amassed into muscle fibers and then into the functional unit, the muscle. Muscles are attached to the body wall, with attachment fibers running through the cuticle and to the epicuticle, where they can move different parts of the body including appendages such as wings. The muscle fiber has many cells with a plasma membrane and outer sheath or sarcolemma. The sarcolemma is invaginated and can make contact with the tracheole carrying oxygen to the muscle fiber.

Franke et al. demonstrated that TMEM43 is localized at the intercalated disc but not at the nuclear envelope. In contrast Christensen et al. have shown that TMEM43 is mainly localized at the sarcolemma.

The intermediate filaments are responsible for forming the structure of the cell cytoskeleton and providing mechanical stability to the cells. Syncoilin co-localizes with α-dystrobrevin at both the neuromuscular junction and sarcolemma while β-Synemin co-localizes with α-dystrobrevin only at the neuromuscular junction. The interaction of α-dystrobrevin and β-synemin provides an additional connection between the intermediate filament system and the dytsrophin-glycoprotein complex. Dysbindin is located at the sarcolemma, and its expression in skeletal muscle is relatively low.

When ACh is degraded by AChE, the receptors are no longer stimulated and the muscle can be repolarised. If enough Na+ enter the muscle fibre, it causes an increase in the membrane potential from its resting potential of -95mV to -50mV (above the threshold potential -55V) which causes an action potential to spread throughout the fibre. This potential travels along the surface of the sarcolemma. The sarcolemma is an excitable membrane that surrounds the contractile structures known as myofibrils that are located deep in the muscle fibre.

The costamere is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane (i.e. the sarcolemma).20: 2327-2331 Costameres are sub-sarcolemmal protein assemblies circumferentially aligned in register with the Z-disk of peripheral myofibrils. They physically couple force-generating sarcomeres with the sarcolemma in striated muscle cells and are thus considered one of several "Achilles' heels" of skeletal muscle, a critical component of striated muscle morphology which, when compromised, is thought to directly contribute to the development of several distinct myopathies.

Functionally, the Anrep effect allows the heart to compensate for an increased end-systolic volume present and the decreased stroke volume that occurs when aortic blood pressure increases. Without the Anrep effect, an increase in aortic blood pressure would create a decrease in stroke volume that would compromise circulation to peripheral and visceral tissues. Sustained myocardial stretch activates tension dependent Na+/H+ exchangers, bringing Na+ ions into the sarcolemma. This increase in Na+ in the sarcolemma reduces the Na+ gradient exploited by sodium-calcium exchanger (NCX) and stops them from working effectively.

In the sarcoplasm are the myofibrils. The myofibrils are long protein bundles about 1 micrometer in diameter each containing myofilaments. Pressed against the inside of the sarcolemma are the unusual flattened myonuclei. Between the myofibrils are the mitochondria.

7th ed. New York: McGraw-Hill Education, 2015. Print. The voltage-gated ion channels of the sarcolemma next to the end plate open in response to the end plate potential. They are sodium and potassium specific and only allow one through.

Exertional rhabdomyolysis results from damage to the intercellular proteins inside the sarcolemma. Myosin and actin break down in the sarcomeres when ATP is no longer available due to injury to the sarcoplasmic reticulum.Efstratiadis G, Voulgaridou A, Nikiforou D, Kyventidis A, Kourkouni E, Vergoulas. Rhabdomyolysis Updated.

These neurotransmitters diffuse across the synapse and bind to specific receptor sites on the cell membrane of the muscle fiber. When enough receptors are stimulated, an action potential is generated and the permeability of the sarcolemma is altered. This process is known as initiation.

Excitation–contraction coupling is the process by which a muscular action potential in the muscle fiber causes the myofibrils to contract. In skeletal muscle, excitation–contraction coupling relies on a direct coupling between key proteins, the sarcoplasmic reticulum (SR) calcium release channel (identified as the ryanodine receptor, RyR) and voltage-gated L-type calcium channels (identified as dihydropyridine receptors, DHPRs). DHPRs are located on the sarcolemma (which includes the surface sarcolemma and the transverse tubules), while the RyRs reside across the SR membrane. The close apposition of a transverse tubule and two SR regions containing RyRs is described as a triad and is predominantly where excitation–contraction coupling takes place.

Desmin is a protein that in humans is encoded by the DES gene. Desmin is a muscle-specific, type IIIThe Human Protein Atlas. Proteinatlas.org. Retrieved on 2013-07-29. intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture.

Hippokratio General Hospital of Thessaloniki. 2007 Jul-Sep; 11(3): 129-137. Damage to the sarcolemma and sarcoplasmic reticulum from direct trauma or high force production causes a high influx of calcium into the muscle fibers increasing calcium permeability. Calcium ions build up in the mitochondria, impairing cellular respiration.

Skeletal muscle includes skeletal muscle fibers, blood vessels, nerve fibers, and connective tissue. Skeletal muscle is wrapped in epimysium, allowing structural integrity of the muscle despite contractions. The perimysium organizes the muscle fibers, which are encased in collagen and endomysium, into fascicles. Each muscle fiber contains sarcolemma, sarcoplasm, and sarcoplasmic reticulum.

CD97 is expressed at the sarcoplasmic reticulum and the peripheral sarcolemma in skeletal muscle. However, lack of CD97 only affects the structure of the sarcoplasmic reticulum, but not the function of skeletal muscle. In addition, CD97 promotes angiogenesis of the endothelium through to α5β1 and αvβ3 integrins, which contributes to cell attachment.

Brooks et al. confirmed this in 1999, when they found that lactate oxidation exceeded that of pyruvate by 10-40% in rat liver, skeletal, and cardiac muscle. In 1990, Roth and Brooks found evidence for the facilitated transporter of lactate, monocarboxylate transport protein (MCT), in the sarcolemma vesicles of rat skeletal muscle.

For the action potential to reach the myofibrils, the action potential travels along the transverse tubules (T-tubules) that connects the sarcolemma and center of the fibre. Later, action potential reaches the sarcoplasmic reticulum which stores the Ca2+ needed for muscle contraction and causes Ca2+ to be released from the sarcoplasmic reticulum.

Most of the force generated by the sarcomeres deep inside the muscle fiber is transmitted perpendicularly to adjacent myofibrils until it reaches the peripheral myofibrils. At that point, the costameric complex channels the force through the sarcolemma to the ECM. The lateral transmission of force by costameres helps maintain uniform sarcomere lengths in adjacent muscle cells that are under the control of different motor units and are therefore not synchronized in their active contractions; restated, if one muscle fiber is actively contracting and an adjacent one is not, the lateral force transmission helps this second fiber to shorten as well. Costameres also transmit forces in the opposite direction, transmitting the forces of external mechanical stress from the sarcolemma to the Z-disk.

External lamina is a structure similar to basal lamina that surrounds the sarcolemma of muscle cells. It is secreted by myocytes and consists primarily of Collagen type IV, laminin and perlecan (heparan sulfate proteoglycan). Nerve cells, including perineurial cells and Schwann cells also have an external lamina-like protective coating.Wheater's Functional Histology, 5th ed.

3D rendering of a skeletal muscle fiber Skeletal muscle fibers show sarcomeres clearly. Muscle fibers are the individual contractile units within a muscle. A single muscle such as the biceps brachii contains many muscle fibers. Another group of cells, the myosatellite cells are found between the basement membrane and the sarcolemma of muscle fibers.

It has a Golgi apparatus near the nucleus, mitochondria just inside the cell membrane (sarcolemma), and a smooth endoplasmic reticulum (specialized for muscle function and called the sarcoplasmic reticulum). While sarcoplasm and myoplasm, viewed etymologically, might seem to be synonyms, they are not. Whereas sarcoplasm is a type of cytoplasm, myoplasm is the entire contractile portion of muscle tissue.

When the body's glycogen is depleted, the ATP concentration diminishes, and the body enters rigor mortis because it is unable to break those bridges. Calcium enters the cytosol after death. Calcium is released into the cytosol due to the deterioration of the sarcoplasmic reticulum. Also, the breakdown of the sarcolemma causes additional calcium to enter the cytosol.

Later, MCT1 was the first of the MCT super family to be identified. The first four MCT isoforms are responsible for pyruvate/lactate transport. MCT1 was found to be the predominant isoform in many tissues including skeletal muscle, neurons, erthrocytes, and sperm. In skeletal muscle, MCT1 is found in the membranes of the sarcolemma, peroxisome, and mitochondria.

This synchronisation of calcium release allows muscle cells to contract more forcefully. In cells lacking T-tubules such as smooth muscle cells, diseased cardiomyocytes, or muscle cells in which T-tubules have been artificially removed, the calcium that enters at the sarcolemma has to diffuse gradually throughout the cell, activating the ryanodine receptors much more slowly as a wave of calcium leading to less forceful contraction. As the T-tubules are the primary location for excitation-contraction coupling, the ion channels and proteins involved in this process are concentrated here - there are 3 times as many L-type calcium channels located within the T-tubule membrane compared to the rest of the sarcolemma. Furthermore, beta adrenoceptors are also highly concentrated in the T-tubular membrane, and their stimulation increases calcium release from the sarcoplasmic reticulum.

Dystrophin protein is found in muscle fiber membrane; its helical nature allows it to act like a spring or shock absorber. Dystrophin links actin in the cytoskeleton and dystroglycans of the muscle cell plasma membrane, known as the sarcolemma (extracellular). In addition to mechanical stabilization, dystrophin also regulates calcium levels. The gene for dystrophin is located on the X chromosome.

Costameres are also involved in protecting the relatively weak and labile sarcolemma from the mechanical stresses of contraction and stretching. The proteins mechanically support the lipid bilayer, and also may facilitate an organized folding of the plasma membrane ("festooning") that minimizes stress on the bilayer during contraction and stretching. Finally, costameres are also involved in the orchestration of mechanically related signaling.

A skeletal muscle fiber is surrounded by a plasma membrane called the sarcolemma, which contains sarcoplasm, the cytoplasm of muscle cells. A muscle fiber is composed of many fibrils, which give the cell its striated appearance. Skeletal muscles are sheathed by a tough layer of connective tissue called the epimysium. The epimysium anchors muscle tissue to tendons at each end, where the epimysium becomes thicker and collagenous.

Excitation-contraction coupling in myocardium relies on sarcolemma depolarization and subsequent Ca2+ entry to trigger Ca2+ release from the sarcoplasmic reticulum. When an action potential depolarizes the cell membrane, voltage-gated Ca2+ channels (e.g., L-type calcium channels) are activated. CICR occurs when the resulting Ca2+ influx activates ryanodine receptors on the SR membrane, which causes more Ca2+ to be released into the cytosol.

The fusion of myoblasts is specific to skeletal muscle (e.g., biceps brachii) and not cardiac muscle or smooth muscle. Myoblasts in skeletal muscle that do not form muscle fibers dedifferentiate back into myosatellite cells. These satellite cells remain adjacent to a skeletal muscle fiber, situated between the sarcolemma and the basement membrane of the endomysium (the connective tissue investment that divides the muscle fascicles into individual fibers).

Once two acetylcholine receptors have been bound, an ion channel is opened and sodium ions are allowed to flow into the cell. The influx of sodium into the cell causes depolarization and triggers a muscle action potential. T tubules of the sarcolemma are then stimulated to elicit calcium ion release from the sarcoplasmic reticulum. It is this chemical release that causes the target muscle fiber to contract.

The principal cytoplasmic proteins are myosin and actin (also known as "thick" and "thin" filaments, respectively) which are arranged in a repeating unit called a sarcomere. The interaction of myosin and actin is responsible for muscle contraction. Every single organelle and macromolecule of a muscle fiber is arranged to ensure form meets function. The cell membrane is called the sarcolemma with the cytoplasm known as the sarcoplasm.

The protein encoded by this gene belongs to the dystrobrevin subfamily and the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC). The DPC consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy.

This gene encodes dystrobrevin beta, a component of the dystrophin-associated protein complex (DPC). The DPC consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and dystrobrevin alpha and beta. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Dystrobrevin beta is thought to interact with syntrophin and the DP71 short form of dystrophin.

The purpose is to reduce the mechanical force on the sarcolemma as a result of muscle contraction. In addition to myoclonus dystonia, problems associated with a dysfunctional DAP complex include Duchenne muscular dystrophy. Upwards of 65 mutations of the SGCE gene are thought to cause myoclonus dystonia. The majority of the mutations lead to a truncated protein product that results in the loss-of-function of the epsilon sarcoglycan protein.

Associated Genetic Factors: PAX7 Mutations in Pax7 will prevent the formation of satellite cells and, in turn, prevent postnatal muscle growth. Satellite cells are described as quiescent myoblasts and neighbor muscle fiber sarcolemma. They are crucial for the repair of muscle, but have a very limited ability to replicate. Activated by stimuli such as injury or high mechanical load, satellite cells are required for muscle regeneration in adult organisms.

The adherens junctions are scattered around dense bands that are circumfering the smooth muscle cell in a rib-like pattern. The dense band (or dense plaques) 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. During contraction, there is a spatial reorganization of the contractile machinery to optimize force development.

Other glycosomes have been found to be attached to myofibrils and mitochondria, rough endoplasmic reticulum, sarcolemma, polyribosomes, or the Golgi apparatus. Glycosome attachment may bestow a functional distinction between them; the glycosomes attached to the myofibrils seem to serve the myosin by providing energy substrates for generation of ATP through glycolysis. The glycosomes in the rough and smooth endoplasmic reticulum make use of its glycogen synthase and phosphorylase phosphatases.

Mice died within two months of transgene expression, mainly due to spontaneous Ventricular tachycardia. Further analysis of N-cadherin knockout mice revealed that the arrhythmias were likely due to ion channel remodeling and aberrant Kv1.5 channel function. These animals showed a prolonged action potential duration, reduced density of inward rectifier potassium channel and decreased expression of Kv1.5, KCNE2 and cortactin combined with disrupted actin cytoskeleton at the sarcolemma.

Myofibrils are composed of repeating sections of sarcomeres, which appear under the microscope as alternating dark and light bands. Sarcomeres are composed of long, fibrous proteins as filaments that slide past each other when a muscle contracts or relaxes. The costamere is a different component that connects the sarcomere to the sarcolemma. Two of the important proteins are myosin, which forms the thick filament, and actin, which forms the thin filament.

The binding of ACh to the receptor can depolarize the muscle fiber, causing a cascade that eventually results in muscle contraction. Neuromuscular junction diseases can be of genetic and autoimmune origin. Genetic disorders, such as Duchenne muscular dystrophy, can arise from mutated structural proteins that comprise the neuromuscular junction, whereas autoimmune diseases, such as myasthenia gravis, occur when antibodies are produced against nicotinic acetylcholine receptors on the sarcolemma.

As a result, the sarcolemma reverses polarity and its voltage quickly jumps from the resting membrane potential of -90mV to as high as +75mV as sodium enters. The membrane potential then becomes hyperpolarized when potassium exits and is then adjusted back to the resting membrane potential. This rapid fluctuation is called the end-plate potentialSaladin, Kenneth S., Stephen J. Sullivan, and Christina A. Gan. Anatomy & Physiology: The Unity of Form and Function.

Certain regions of the sarcolemma penetrate deep into the cell. These are known as transverse-tubules (t-tubules); which are also found in skeletal muscle cells) and allow for the action potential to travel into the centre of the cell.Hong, T., Shaw, R.M., Institute, C.-S.H., Center, C.-S.M., Angeles, L., California and Angeles, C.L. (2017) ‘Cardiac T-Tubule Microanatomy and function’, Reviews, 97(1), pp. 227–252. doi: 10.1152/physrev.00037.2015.

The overall process is initiated by an external signal, typically through an action potential stimulating the muscle, which contains specialized cells whose interiors are rich in actin and myosin filaments. The contraction-relaxation cycle comprises the following steps: # Depolarization of the sarcolemma and transmission of an action potential through the T-tubules. # Opening of the sarcoplasmic reticulum’s Ca2+ channels. # Increase in cytosolic Ca2+ concentrations and the interaction of these cations with troponin causing a conformational change in its structure.

Cardiac muscle cells branch freely and are connected by junctions known as intercalated discs which help the synchronized contraction of the muscle. The sarcolemma (membrane) from adjacent cells bind together at the intercalated discs. They consist of desmosomes, specialized linking proteoglycans, tight junctions, and large numbers of gap junctions that allow the passage of ions between the cells and help to synchronize the contraction. Intercellular connective tissue also helps to strongly bind the cells together, in order to withstand the forces of contraction.

In skeletal muscle dystrophy, mitochondrial dysfunction gives rise to an amplification of stress-induced cytosolic calcium signals and an amplification of stress-induced reactive-oxygen species production. In a complex cascading process that involves several pathways and is not clearly understood, increased oxidative stress within the cell damages the sarcolemma and eventually results in the death of the cell. Muscle fibers undergo necrosis and are ultimately replaced with adipose and connective tissue. DMD is inherited in an X-linked recessive pattern.

In the human fetus during muscle differentiation, utrophin is found at the sarcolemma. It disappears when the fetus begins to express dystrophin. Utrophin expression is dramatically increased in patients with Duchenne's muscular dystrophy (and female carriers), both in those muscle fibers lacking dystrophin and in rare, revertant fibers that express dystrophin. No reports have yet associated mutation in the utrophin gene with disease, but it does not seem to play a critical role in development, since mice without utrophin develop normally.

Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in cardiac muscle at Z-disc structures, costameres and at the sarcolemma membrane. Mutations in alpha II- spectrin have been associated with early infantile epileptic encephalopathy-5, and alpha II-spectrin may be a valuable biomarker for Guillain–Barré syndrome and infantile congenital heart disease.

Beta-sarcoglycan is a protein that in humans is encoded by the SGCB gene. The dystrophin-glycoprotein complex (DGC) is a multisubunit protein complex that spans the sarcolemma and provides structural linkage between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. There are 3 main subcomplexes of the DGC: the cytoplasmic proteins dystrophin (DMD; MIM 300377) and syntrophin (SNTA1; MIM 601017), the alpha- and beta- dystroglycans (see MIM 128239), and the sarcoglycans (see, e.g., SGCA; MIM 600119) (Crosbie et al.

Intercalated discs are part of the cardiac muscle sarcolemma and they contain gap junctions and desmosomes. The cardiac syncytium is a network of cardiomyocytes connected by intercalated discs that enable the rapid transmission of electrical impulses through the network, enabling the syncytium to act in a coordinated contraction of the myocardium. There is an atrial syncytium and a ventricular syncytium that are connected by cardiac connection fibres. Electrical resistance through intercalated discs is very low, thus allowing free diffusion of ions.

Parasympathetic nerves work by releasing a neurotransmitter called acetylcholine (ACh) which binds to specific receptor (M2 muscarinic receptor) on the sarcolemma of both SAN cells and ventricular cells. This again activates a G-protein. However this G-protein works by inhibiting, the cAMP pathway, therefore, preventing the sympathetic nervous system from increasing heart rate. As well as this, in the SAN, the G-protein activates specific potassium channel, that opposes action potential initiation (see SAN for more details), thus slowing heart rate.

Details of intercalated discs Cardiomyocytes, are considerably shorter and have smaller diameters than skeletal myocytes. Cardiac muscle (like skeletal muscle) is characterized by striations – the stripes of dark and light bands resulting from the organised arrangement of myofilaments and myofibrils in the sarcomere along the length of the cell. T (transverse) tubules are deep invaginations from the sarcolemma (cell membrane) that penetrate the cell, allowing the electrical impulses to reach the interior. In cardiac muscle the T-tubules are only found at the Z-lines.

These viral proteases can also act on host proteins exerting negative effects on the residing cell. Enteroviral protease 2A can cleave the cytoskeletal dystrophin protein in cardiomyocytes disrupting the dystrophin glycoprotein (DCG) complex. The cleavage site of dystrophin by protease 2A occurs in the hinge 3 region of the protein resulting a disruption of DCG complex and loss of sarcolemma integrity and increasing myocyte permeability. This eventually results in similar cardiac deformities observed in dilated cardiomyopathy caused by hereditary defects in dystrophin in DMD patients.

DMD is inherited in a X-linked recessive manner DMD is caused by a mutation of the dystrophin gene at locus Xp21, located on the short arm of the X chromosome. Dystrophin is responsible for connecting the cytoskeleton of each muscle fiber to the underlying basal lamina (extracellular matrix), through a protein complex containing many subunits. The absence of dystrophin permits excess calcium to penetrate the sarcolemma (the cell membrane). Alterations in calcium and signalling pathways cause water to enter into the mitochondria, which then burst.

Two common stimuli for eliciting smooth muscle contraction are circulating epinephrine and activation of the sympathetic nervous system (through release of norepinephrine) that directly innervates the muscle. These compounds interact with cell surface adrenergic receptors. Such stimuli result in a signal transduction cascade that leads to increased intracellular calcium from the sarcoplasmic reticulum through IP3-mediated calcium release, as well as enhanced calcium entry across the sarcolemma through calcium channels. The rise in intracellular calcium complexes with calmodulin, which in turn activates myosin light-chain kinase.

The core proteins of DGC are dystrophin, the sarcoglycans (including alpha, beta, gamma, and lambda sarcoglycan), sarcospan, dystroglycan (alpha and beta), and syntrophin. These proteins are thought to play an important role in maintaining the structural integrity of sarcolemma during contraction and stretching, and loss of these core proteins results in progressive contraction induced damage. The vinculin and talin components of the integrin-vinculin-talin complex are cytoskeletal proteins physically anchored to the costamere as a whole via the integrin components, which are transmembrane proteins that interact directly with filamin C of the Z disk.

As cations flow into the postsynaptic cell, this causes a depolarization, as the membrane voltage increases above normal resting potential. If the signal is of sufficient magnitude, than an action potential will be generated post synaptically. The action potential will propagate through the sarcolemma to the interior of the muscle fibers eventually leading to an increase in intracellular calcium levels and subsequently initiating the process of Excitation–contraction coupling. Once coupling begins it allows the sarcomeres of the muscles to shorten, thus leading to the contraction of the muscle.

Dense bodies appear darker under an electron microscope, and so they are sometimes described as electron dense.Ultrastructure of Smooth Muscle, Volume 8 of Electron Microscopy in Biology and Medicine, Editor P. Motta, Springer Science & Business Media, 2012, . (p. 163 ) The intermediate filaments are connected to other intermediate filaments via dense bodies, which eventually are attached to adherens junctions (also called focal adhesions) in the cell membrane of the smooth muscle cell, called the sarcolemma. The adherens junctions consist of large number of proteins including α-actinin, vinculin and cytoskeletal actin.

RYR1 functions as a calcium release channel in the sarcoplasmic reticulum, as well as a connection between the sarcoplasmic reticulum and the transverse tubule. RYR1 is associated with the dihydropyridine receptor (L-type calcium channels) within the sarcolemma of the T-tubule, which opens in response to depolarization, and thus effectively means that the RYR1 channel opens in response to depolarization of the cell. RYR1 plays a signaling role during embryonic skeletal myogenesis. A correlation exists between RYR1-mediated Ca2+ signaling and the expression of multiple molecules involved in key myogenic signaling pathways.

In cardiac muscle, N-cadherin is found at intercalated disc structures which provide end-on cell–cell connections that facilitate mechanical and electrical coupling between adjacent cardiomyocytes. Within intercalated discs are three types of junctions: adherens junctions, desmosomes and gap junctions; N-cadherin is an essential component in adherens junctions, which enables cell–cell adhesion and force transmission across the sarcolemma. N-cadherin complexed to catenins has been described as a master regulator of intercalated disc function. N-cadherin appears at cell–cell junctions prior to gap junction formation, and is critical for normal myofibrillogenesis.

Filamin-C is a 290.8 kDa protein composed of 2725 amino acids. Filamin-C, like the ubiquitously-expressed isoform Filamin-A, have an N-terminal filamentous actin-binding domain, followed by a lengthy C-terminal self-association domain containing a series of immunoglobulin-like domains, and a membrane glycoprotein-binding domain. Filamin-C interacts with γ-sarcoglycan and δ-sarcoglycan at the sarcolemma; myotilin and FATZ/calsarcin/myozenin at Z-lines, as well as LL5β. Filamin-C has also been shown to interact with INPPL1, KCND2, and MAP2K4.

A special case of a chemical synapse is the neuromuscular junction, in which the axon of a motor neuron terminates on a muscle fiber. In such cases, the released neurotransmitter is acetylcholine, which binds to the acetylcholine receptor, an integral membrane protein in the membrane (the sarcolemma) of the muscle fiber. However, the acetylcholine does not remain bound; rather, it dissociates and is hydrolyzed by the enzyme, acetylcholinesterase, located in the synapse. This enzyme quickly reduces the stimulus to the muscle, which allows the degree and timing of muscular contraction to be regulated delicately.

Activation of the L-type calcium channel allows calcium to pass into the cell. T-tubules contain a higher concentration of L-type calcium channels than the rest of the sarcolemma and therefore the majority of the calcium that enters the cell occurs via T-tubules. This calcium binds to and activates a receptor, known as a ryanodine receptor, located on the cell's own internal calcium store, the sarcoplasmic reticulum. Activation of the ryanodine receptor causes calcium to be released from the sarcoplasmic reticulum, causing the muscle cell to contract.

These action potentials travel along the cell membrane (sarcolemma), as impulses, passing from one cell to the next through channels, in structures known as gap junctions.Kurtenbach, S. and Zoidl, G. (2014) ‘Gap junction modulation and its implications for heart function’, 5. The speed of conduction of the action potential varies at different parts of the heart (for more information, see electrical conduction system of the heart). This is important as it means that once the atria have contracted, there is a slight delay which enables the ventricles to fill with blood before they contract.

Heart rate is affected by nerves. Sympathetic nerves, coming from the spinal cord, increase heart rate, whereas parasympathetic nerves (for example the vagus nerves) work to decrease it. Sympathetic nerves work by releasing a protein (neurotransmitter) called noradrenaline which binds to a specific receptor (beta 1 adrenoceptor) located in the sarcolemma and the t-tubule membrane of cardiac cells. This activates a protein, called a G-protein and results in a series of reactions (known as a cyclic AMP pathway) that leads to the production of a molecule called cAMP (cyclic adenosine monophosphate).

Dystrophin supports muscle fiber strength, and the absence of dystrophin reduces muscle stiffness, increases sarcolemmal deformability, and compromises the mechanical stability of costameres and their connections to nearby myofibrils. This has been shown in recent studies where biomechanical properties of the sarcolemma and its links through costameres to the contractile apparatus were measured, and helps to prevent muscle fiber injury. Movement of thin filaments (actin) creates a pulling force on the extracellular connective tissue that eventually becomes the tendon of the muscle. The dystrophin associated protein complex also helps scaffold various signalling and channel proteins, implicating the DAPC in regulation of signalling processes.

Epsilon sarcoglycan is a membrane protein that can be found in the liver, lungs, kidney, and spleen, but is most prevalent in muscle and neuronal cells. Its prevalence in both muscle fibers and the synapses of neurons suggest why symptoms of both myoclonus and dystonia appear from the improperly functioning protein. Recessive mutations in the other sarcoglycans also result in muscular disorders, further supporting that mutations in the SGCE gene cause myoclonus dystonia. Epsilon sarcoglycan itself is part of the dystrophin-associated protein (DAP) complex that binds the sarcolemma of muscle cells to the extracellular connective tissue.

The dystrophin-associated glycoprotein (DAG) complex, also referred to as the dystrophin-glycoprotein complex (DGC), contains various integral and peripheral membrane proteins such as dystroglycans and sarcoglycans, which are thought to be responsible for linking the internal cytoskeletal system of individual myofibers to structural proteins within the extracellular matrix (such as collagen and laminin). Therefore, it is one of the features of the sarcolemma which helps to couple the sarcomere to the extracellular connective tissue as some experiments have shown. Desmin protein may also bind to the DAG complex, and regions of it are known to be involved in signaling.

The sarcoglycans are a family of transmembrane proteins (α, β, γ, δ or ε) involved in the protein complex responsible for connecting the muscle fibre cytoskeleton to the extracellular matrix, preventing damage to the muscle fibre sarcolemma through shearing forces. The dystrophin glycoprotein complex (DGC) is a membrane-spanning complex that links the interior cytoskeleton to the extracellular matrix in muscle. The sarcoglycan complex is a subcomplex within the DGC and is composed of several muscle-specific, transmembrane proteins (alpha-, beta-, gamma-, delta- and zeta-sarcoglycan). The sarcoglycans are asparagine-linked glycosylated proteins with single transmembrane domains.

Ca2+ ions accumulate inside the sarcolemma as a result and are uptaken by sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pumps. Calcium induced calcium release (CICR) from the sarcoplasmic reticulum is increased upon stimulation of the cardiac myocyte by an action potential. This leads to an increase in the force of contraction of the cardiac muscle to try and increase stroke volume and cardiac output to maintain tissue perfusion.On the other hand, it has been proposed that the Anrep effect may be a spurious effect resulting from the recovery of the myocardium from a transient ischemia arising from the abrupt increase in blood pressure.

The sarcolemma also contains caveolae, which are microdomains of lipid rafts specialized to cell signaling events and ion channels. These invaginations in the sarcoplasm 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 close to sarcoplasmic reticulum or mitochondria, and have been proposed to organize signaling molecules in the membrane.

Alternate splicing of alpha II-spectrin has been documented and results in multiple transcript variants; specifically, cardiomyocytes have four identified alpha II-spectrin splice variants. As opposed to alpha I-spectrin that is principally found in erythrocytes, alpha II-spectrin is expressed in most tissues. In cardiac tissue, alpha II-spectrin is found in myocytes at Z-discs, costameres, and the sarcolemma membrane, and in cardiac fibroblasts along the surface of the cytoskeletal network. Alpha II-spectrin most commonly exists in a heterodimer with alpha II and beta II spectrin subunits; and dimers typically self- associate and heterotetramerize.

This influx of sodium ions generates the EPP (depolarization), and triggers an action potential which travels along the sarcolemma and into the muscle fiber via the T-tubules (transverse tubules) by means of voltage- gated sodium channels. The conduction of action potentials along the T-tubules stimulates the opening of voltage-gated Ca2+ channels which are mechanically coupled to Ca2+ release channels in the sarcoplasmic reticulum. The Ca2+ then diffuses out of the sarcoplasmic reticulum to the myofibrils so it can stimulate contraction. The endplate potential is thus responsible for setting up an action potential in the muscle fiber which triggers muscle contraction.

The action potential in a normal skeletal muscle cell is similar to the action potential in neurons. Action potentials result from the depolarization of the cell membrane (the sarcolemma), which opens voltage-sensitive sodium channels; these become inactivated and the membrane is repolarized through the outward current of potassium ions. The resting potential prior to the action potential is typically −90mV, somewhat more negative than typical neurons. The muscle action potential lasts roughly 2–4 ms, the absolute refractory period is roughly 1–3 ms, and the conduction velocity along the muscle is roughly 5 m/s.

The idea of a cellular structure that later became known as a T-tubule was first proposed in 1881. The very brief time lag between stimulating a striated muscle cell and its subsequent contraction was too short to have been caused by a signalling chemical travelling the distance between the sarcolemma and the sarcoplasmic reticulum. It was therefore suggested that pouches of membrane reaching into the cell might explain the very rapid onset of contraction that had been observed. It took until 1897 before the first T-tubules were seen, using light microscopy to study cardiac muscle injected with India ink.

Acetylcholine receptors 5\. mitochondrion In order to transduce an excitatory signal to the muscle, an indication must transduce from the presynaptic neuron's axon terminal, travel across the synaptic cleft and be received correctly in the post synaptic muscle tissue's motor end plate to produce the desired effect, at the right intensity. The signal that leaves the presynaptic neuron is in the form of Acetylcholine (Ach), a molecule that is released from stored vesicles at the terminal end of the neuron. Ach travels across the space of the synaptic cleft, to an Ach receptors on the sarcolemma of the motor end plate.

In myocytes, sarcomeres adhere to the sarcolemma via costameres, which align at Z-discs and M-lines. The two primary cytoskeletal components of costameres are desmin intermediate filaments and gamma-actin microfilaments. It has been shown that gamma-actin interacting with another costameric protein dystrophin is critical for costameres forming mechanically strong links between the cytoskeleton and the sarcolemmal membrane. Additional studies have shown that gamma-actin colocalizes with alpha-actinin and GFP-labeled gamma actin localized to Z-discs, whereas GFP-alpha-actin localized to pointed ends of thin filaments, indicating that gamma actin specifically localizes to Z-discs in striated muscle cells.

This finding was coordinate with enhanced expression of pro-survival proteins, survivin and Bcl-2, and vascular endothelial growth factor while promoting the differentiation of cardiac fibroblasts into myofibroblasts. These findings suggest that beta-catenin can promote the regeneration and healing process following myocardial infarction. In a spontaneously-hypertensive heart failure rat model, investigators detected a shuttling of beta-catenin from the intercalated disc/sarcolemma to the nucleus, evidenced by a reduction of beta-catenin expression in the membrane protein fraction and an increase in the nuclear fraction. Additionally, they found a weakening in the association between glycogen synthase kinase-3β and beta-catenin, which may indicate altered protein stability.

Genes coding for the enzyme are primarily expressed in the liver, in the kidney cortex and (to a lesser extent) in the β-cells of the pancreatic islets and intestinal mucosa (especially during times of starvation). According to Surholt and Newsholme, Glc 6-Pase is present in a wide variety of muscles across the animal kingdom, albeit at very low concentrations. Thus, the glycogen that muscles store is not usually available for the rest of the body's cells because glucose 6-phosphate cannot cross the sarcolemma unless it is dephosphorylated. The enzyme plays an important role during periods of fasting and when glucose levels are low.

Synaptic transmission at the neuromuscular junction begins when an action potential reaches the presynaptic terminal of a motor neuron, which activates voltage-gated calcium channels to allow calcium ions to enter the neuron. Calcium ions bind to sensor proteins (synaptotagmin) on synaptic vesicles, triggering vesicle fusion with the cell membrane and subsequent neurotransmitter release from the motor neuron into the synaptic cleft. In vertebrates, motor neurons release acetylcholine (ACh), a small molecule neurotransmitter, which diffuses across the synaptic cleft and binds to nicotinic acetylcholine receptors (nAChRs) on the cell membrane of the muscle fiber, also known as the sarcolemma. nAChRs are ionotropic receptors, meaning they serve as ligand-gated ion channels.

An important role has been implicated for N-RAP in myofibrilar organization during cardiomyocyte development. It is clear that NRAP is critical for normal α-actinin-dependent organization of myofibrils in cardiomyocytes, as knock-down of N-RAP protein levels causes myofbrillar disassembly in embryonic cardiomyocytes. Specifically, studies suggest that NRAP super repeats may be an essential scaffold for organizing alpha-actinin and actin into sarcomereic I-Z-I complexes in premyofibrils, and dynamic imaging studies have shown that N-RAP departs from the I-Z-I complexes upon completion of actin thin filament assembly. In adult cardiac muscle, N-RAP colocalizes to intercalated discs, where it functions to anchor terminal actin filaments to the sarcolemma.

Though αE-catenin exhibits substantial expression in cardiac muscle, αE-catenin is most well known for role in metastasizing tumor cells. αE-catenin also plays a role in epithelial tissue, both at adherens junctions and in signaling pathways. In cardiomyocytes, αE-catenin is present in cell to cell regions known as adherens junctions which lie within intercalated discs; these junctions anchor the actin cytoskeleton to the sarcolemma and provide strong cell adhesion. Functional αE-catenin is required for normal embryonic development, as a mutation eliminating the C-terminal 1/3 of the protein resulting in a complete loss-of-function phenotype showed disruption of the trophoblast epithelium and arrested development at the blastocyst stage.

Costameres are highly complex networks of proteins and glycoproteins, and can be considered as consisting of two major protein complexes: the dystrophin-glycoprotein complex (DGC) and the integrin-vinculin-talin complex. The sarcoglycans of the DGC and the integrins of the integrin-vinculin-talin complex attach directly to filamin C, a component of the Z-disk, linking these protein complexes of costameres to complexes of the Z-disk. Restated, filamin C physically links the two complexes that constitute the costamere to sarcomeres by interacting with the sarcoglycans in the DGC and the integrins of the integrin-vinculin- talin complex. The DGC consists of peripheral and integral proteins that physically traverse the sarcolemma and connect the ECM to the F-actin based cytoskeleton.

Generally, small hydrophobic molecules can readily cross phospholipid bilayers by simple diffusion. Particles that are required for cellular function but are unable to diffuse freely across a membrane enter through a membrane transport protein or are taken in by means of endocytosis, where the membrane allows for a vacuole to join onto it and push its contents into the cell. Many types of specialized plasma membranes can separate cell from external environment: apical, basolateral, presynaptic and postsynaptic ones, membranes of flagella, cilia, microvillus, filopodia and lamellipodia, the sarcolemma of muscle cells, as well as specialized myelin and dendritic spine membranes of neurons. Plasma membranes can also form different types of "supramembrane" structures such as caveolae, postsynaptic density, podosome, invadopodium, desmosome, hemidesmosome, focal adhesion, and cell junctions.

F. Spencer Gaskin, Kazuhiro Kamada, Mozow Yusof, William Durante, Garrett Gross, and Ronald J. Korthuis. AICAR Preconditioning Prevents Postischemic Leukocyte Rolling and Adhesion: Role of KATP Channels and Heme Oxygenase Microcirculation 16:2, 167-176 (2009) AICAR- dependent preconditioning is also mediated by an ATP-sensitive potassium channel and hemeoxygenase-dependent mechanism. It increases AMPK-dependent recruitment of ATP-sensitive K channels to the sarcolemma causing the action potential duration to shorten, and preventing calcium overload during reperfusion.Sukhodub, A., Jovanovic, S., Du, Q., Budas, G., Clelland, A.K., Shen, M., Sakamoto, K., Tian, R. & Jovanovic, A. AMP-activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ATP-sensitive K(+) channels. J Cell Physiol 210, 224–236. (2007).

This mutation causes a conformational shift in the haemoglobin molecule from the low-oxygen to the high-oxygen affinity form. The left-ventricle of the heart, which is responsible for pumping oxygenated blood to the body via systemic circulation, has significantly more capillaries in bar-headed geese than in lowland birds, maintaining oxygenation of cardiac muscle cells and thereby cardiac output. Compared to lowland birds, mitochondria (the main site of oxygen consumption) in the flight muscle of bar-headed geese are significantly closer to the sarcolemma, decreasing the intracellular diffusion distance of oxygen from the capillaries to the mitochondria. Bar-headed geese have a slightly larger wing area for their weight than other geese, which is believed to help them fly at high altitudes.

In skeletal muscle cells, however, the L-type calcium channel is directly attached to the ryanodine receptor on the sarcoplasmic reticulum allowing activation of the ryanodine receptor directly without the need for an influx of calcium. The importance of T-tubules is not solely due to their concentration of L-type calcium channels, but lies also within their ability to synchronise calcium release within the cell. The rapid spread of the action potential along the T-tubule network activates all of the L-type calcium channels near-simultaneously. As T-tubules bring the sarcolemma very close to the sarcoplasmic reticulum at all regions throughout the cell, calcium can then be released from the sarcoplasmic reticulum across the whole cell at the same time.

When an action potential causes the release of many acetylcholine vesicles, acetylcholine diffuses across the neuromuscular junction and binds to ligand-gated nicotinic receptors (non- selective cation channels) on the muscle fiber. This allows for increased flow of sodium and potassium ions, causing depolarization of the sarcolemma (muscle cell membrane). The small depolarization associated with the release of acetylcholine from an individual synaptic vesicle is called a miniature end- plate potential (MEPP), and has a magnitude of about +0.4mV. MEPPs are additive, eventually increasing the end-plate potential (EPPs) from about -100mV up to the threshold potential of -60mV, at which level the voltage- gated ion channels in the postsynaptic membrane open, allowing a sudden flow of sodium ions from the synapse and a sharp spike in depolarization.

Plakophilin 2 functions to link cadherins to intermediate filaments in the cytoskeleton. In cardiomyocytes, plakophilin-2 is found at desmosome structures within intercalated discs, which link adjacent sarcolemmal membranes together. The desmosomal protein, desmoplakin, is the core constituent of the plaque which anchors intermediate filaments to the sarcolemma by its C-terminus and indirectly to sarcolemmal cadherins by its N-terminus, facilitated by plakoglobin and plakophilin-2. Plakophilin is necessary for normal localization and content of desmoplakin to desmosomes, which may in part be due to the recruitment of protein kinase C alpha to desmoplakin. Ablation of PKP2 in mice severely disrupts normal heart morphogenesis. Mutant mice are embryonic lethal and exhibit deficits in the formation of adhering junctions in cardiomyocytes, including the dissociation of desmoplakin and formation of cytoplasmic granular aggregates around embryonic day 10.5-11.

Mice died within 1 month of birth and had severe muscle degeneration, suggesting that the roles of these proteins may overlap to maintain the stability of the sarcolemma. Moreover, the double knockout of dystrophin and alpha-7 integrin produced a Duchenne muscular dystrophy-like phenotype, and demonstrated that alterations in alpha-7 integrin affect the pathological changes observed in dystrophin deficiencies. In support of this notion, AAV overexpression of ITGA7 in skeletal muscle of Duchenne muscular dystrophy (DMD) mice showed a significant protective effect against adverse functional parameters associated with DMD, combined with a reversal of these negative features, suggesting that alpha-7 integrin may be a potential therapeutic candidate to treat Duchenne muscular dystrophy. Studies employing mutant alpha-7 integrin constructs have shown that the cytoplasmic tail of alpha-7B integrin is essential for regulation of lamellipodia formation and regulation of cell mobility regulation via laminin-1/E8 and p130(CAS)/Crk complex formation.