n. The thin, transparent, extensible membrane covering every striated muscle fiber
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What is the sarcolemma? It is the thin, transparent, extensible plasma membrane of the muscle cell. It consists of a cell membrane (plasma membrane) and an outer coat made up of a thin layer of polysaccharide (glycocalyx) material with numerous thin collagen fibrils. Etymologically, what do you mean by sarcolemma? ‘Sarco’ comes from the Greek (sarx) meaning “flesh”, and ‘lemma’ comes from the Greek meaning “sheath”.
Characteristics of Sarcolemma
The sarcolemma anatomy can be defined as the plasma membrane of a muscle cell or the plasma membrane of a muscle fiber. Muscle cells are also known as muscle fibers due to their long, cylindrical shape.
The sarcolemma is covered by a glycocalyx. How do we define glycocalyx? The glycocalyx is a coating covering the cell membrane. It is composed of glycosaminoglycans (GAGs), proteoglycans, and other glycoproteins that consist of acidic oligosaccharides with sialic acids at the terminal position. Proteins associated with the glycocalyx function as transmembrane proteins that help link the membrane to the cytoskeleton of the cell. This keeps the structure of the membrane secure and allows signal transduction between the intracellular and extracellular components.
The sarcolemma can be excited electrically leading to the activation of muscle fibers by signals from motor nerves. The sarcolemma contains ion-conducting pathways and channels through which sodium, potassium, calcium, and chloride flow selectively and non-selectively.
These membrane pathways can open in response to specific molecules (ligands), transmitters, or when changes in voltage occur. The sarcolemma uses naturally-occurring regulatory processes to close these pathways.
Just outside the sarcolemma, in contact with the glycocalyx is the basement membrane. This serves to prevent further diffusion of electrolytes as well as maintaining support and shape for the muscle fibers.
Is sarcolemma a connective tissue? No, it is not connective tissue. The sarcolemma is the plasma membrane.
The sarcolemma is described as having two layers. The first is the plasma membrane, which is a structure of similar biochemical composition to the general plasma membrane found in eukaryotic cells. The second layer is the glycocalyx, which is in contact with the basement membrane. The basement membrane is rich in collagen fibrils and proteins that allow the muscle fibers to adhere to it. The cytoskeleton of the muscle cell, which consists of a large amount of the protein actin, is connected to the basement membrane through transmembrane proteins in the plasma membrane. The ends of the muscle fibers fuse with tendon fibers, which in turn collect into bundles to form muscle tendons. This attaches muscle fibers to the bone.
There are 3 layers of connective tissue in muscles. These are the epimysium, the perimysium, and the endomysium. The outermost layer of connective tissue surrounding a skeletal muscle is the epimysium. The perimysium wraps around bundles of muscle fibers (fascicles) and the endomysium wraps around the individual muscle fibers. So, what is the difference between the sarcolemma vs endomysium? It is important not to confuse these terms. The sarcolemma is the cell membrane of the muscle fiber, and the endomysium is the connective tissue layer over the muscle fiber. Figure 2 shows the locations of the 3 layers of connective tissue.
To understand the structure and function of the sarcolemma, we must first understand the structure of striated muscle tissue. Within muscle fibers, myofibrils are found running the length of the cell. Myofibrils can be described as units of a muscle cell made up of organized proteins consisting of sarcomeres. Hundreds to thousands of myofibrils can be found in each muscle fiber.
There are 2 types of myofibrils that are either made up of thick filaments or thin filaments. The protein actin predominantly forms the thin filaments along with proteins tropomyosin and troponin. The protein myosin forms the thick filaments. These filaments overlap to form patterns that can be viewed under a microscope (striations).
Actin and myosin are the proteins involved in muscle contraction. These thin and thick filaments arrange to form bands known as A-bands and I-bands. “A” stands for Anisotropic (because the filaments are stronger in one direction than the other) and “I” stands for isotropic (because they have the same physical properties in any direction). The A band contains an H-zone where no overlap between the thin and thick filaments occurs. It consists only of the thick filament and allows muscle contraction by becoming shorter.
A sarcomere is a structural unit of striated muscle tissue. Sarcomeres are repeating units that occur between each Z line (or Z disc). The Z line is the boundary between each sarcomere. The sarcomere is composed of myofibrils. The M line is in the center of the sarcomere and is the attachment site for the thick filaments. The M line is composed of proteins myomesin, titin, obscurin, and obsl1. Figures 3 and 4 show the structure of a sarcomere indicating the different filaments and bands.
Now we have looked at the structure of the muscle tissue. We can understand more about the plasma membrane of the muscle cells. As mentioned earlier, the plasma membrane of a skeletal muscle fiber is called the sarcolemma. The sarcolemma invaginates into the cytoplasm of the muscle cell (sarcoplasm). This forms membranous tubules that pass across the muscle cells. These are called transverse tubules (or ‘T tubules’). The T- tubules contain extracellular fluid, which is high in both calcium and sodium ions.
Inside the muscle fibers, the T-tubules lie close to enlarged areas of the sarcoplasmic reticulum known as terminal cisternae. Two terminal cisternae found on either side of a T-tubule is known as a triad. There are thousands of triads in each muscle fiber. The sarcoplasmic reticulum is found surrounding the myofibrils and is made up of membrane-bound tubules. The sarcoplasmic reticulum functions as a calcium store. More information regarding the sarcolemma function is described in more detail below. Figure 5 shows the anatomical relationship of the T-tubules, terminal cisternae, and the sarcoplasmic reticulum, as well as a microscopic image of a triad.
The Function of the Sarcolemma
What is the function of sarcolemma? As the muscle cell membrane, the sarcolemma functions as a barrier between the extracellular and intercellular parts of the muscle fiber cells. It can do this because the membrane is lipid in nature, thereby it separates the fluids of the intracellular and extracellular spaces and only allows water in through aquaporin channels. The membrane contains ion pumps as in other cell membranes in the body, allowing for ion gradients to be created to use up ATP.
The T-tubule membrane portion of the sarcolemma is highly plastic and therefore provides stability during muscle contraction. Studies have also shown that T tubules are involved in water balance and cell volume regulation, recovery from muscle fatigue as well as transport of molecules. The T-tubules also have an important role involved in the transmission of action potentials which will be discussed later.
The structure and design of the sarcolemma are essential for receiving and conducting stimuli. During the resting state, the sarcolemma keeps the inside of the muscle fiber at a negative potential compared to the extracellular fluid. It pumps out more sodium ions than it takes in potassium ions. Therefore, the sarcoplasm has a higher potassium concentration but a lower sodium concentration than the extracellular space. In terms of charge, this means that the inside of the sarcolemma has a negative charge, and the extracellular space has a positive charge.
Embedded in the sarcolemma are voltage-gated sodium channels, sodium and potassium ATPase pumps, and voltage-gated potassium pumps. These channels and pumps are responsible for maintaining a negative potential. The sarcolemma is also semi-permeable and allows diffusion of ions down their electrochemical gradients.
What initiates an action potential on a muscle cell?
An action potential can be described as a sudden change of membrane resting potential. The neurotransmitter acetylcholine (ACh) initiates a cascade of events as it is released from neuromuscular junctions at the pre-synaptic nerve terminals. ACh binds to receptors on the sarcolemma known as nicotinic acetylcholine receptors (nAChRs).
This binding allows the flow of sodium down its concentration gradient creating an action potential leading to depolarization of the muscle fiber. Put simply, the voltage difference is reduced between the inside of the sarcolemma and outside in the extracellular matrix by sodium ions moving into the muscle and potassium ions moving out.
Repolarization of the membrane occurs when the membrane returns to its resting state. Due to the positive charge on the inside of the membrane, the voltage-gated sodium channels close and the voltage-gated potassium channels open, but only when the sarcoplasm has reached its maximum positive charge. Positively charged potassium ions can then flow back out into the extracellular space outside the muscle cell this allows a decrease in positive charge and the sarcolemma is said to be repolarized. During repolarization, and a short time after, the sodium channels need to go back to their resting state and the membrane cannot be repolarized again. This is known as the refractory period. Figure 6 shows the cascade of events involved in depolarization of the sarcolemma.Figure 6. Depolarization events in the sarcolemma. Credit: RPayne0216, Lecture Exam 3: steps in summary of events in generation and propagation of an action potential in a skeletal muscle fiber, from Quizlet.
The Importance of T-tubules and Triads
The action potential travels from the sarcolemma down a T-tubule and into the sarcoplasmic reticulum. As it does so, the release of calcium ions is stimulated from the terminal cisternae of the sarcoplasmic reticulum. The calcium ions then bind with troponin (a globular protein complex found in thin filaments along with actin and tropomyosin). Actin sites are then exposed, and muscle contraction can take place. The action potential can be described as a wave flowing away from the neuromuscular junction along the sarcolemma.
The signal communication from the sarcolemma to the muscle proteins is aided by calcium ions. Muscle fibers can quickly release and take up calcium ions. Because myofibrils can be millimeters or even up to centimeters in length, the triads structure operates to connect the sarcolemma with the calcium stores. This helps to overcome the spatial limits of using calcium as a messenger.
The signal communication from the sarcolemma to the myofibrils to begin muscle contraction is known as excitation-contraction (E-C) coupling. This term was first described by Alexander Sandow in 1952. The T-tubules and the sarcoplasmic reticulum are vital for E-C coupling. The T-tubules carry the action potential along their surface causing the depolarization of the cell interior. The terminal cisternae of the sarcoplasmic reticulum have high concentrations of calcium ions inside.
As the T-tubules conduct the action potential, the terminal cisternae that are close by open voltage-dependent release channels. These events allow the diffusion of calcium into the sarcoplasm. This increases the amount of calcium that is available to bind to troponin, resulting in its conformational change and tropomyosin moves on the actin filament. This reveals the myosin-binding site on the actin molecules.
When the concentration of calcium is depleted, the muscle contraction will stop. Calcium levels can be restored to their resting state by being actively transported back into the sarcoplasmic reticulum. The resting-state prevents muscle contraction by keeping the calcium ions retained in the sarcoplasmic reticulum and away from the sarcoplasm. Figure 7 shows this sequence of events.
Diseases of skeletal muscle that lead to muscle weakness and degeneration can be caused by inherited muscular dystrophy diseases. These are progressive disorders where healthy muscle fibers are replaced by fat and fibrosis. Respiratory failure can also happen if the disease involves the breathing muscles.
Duchenne muscular dystrophy (DMD) is one such example and one of the more common forms of muscular dystrophy. It affects males and is caused by a mutation on the dystrophin gene on the X chromosome. Becker muscular dystrophy is also caused by mutations on the gene that codes dystrophin. This disease has a later onset than DMD.
Dystrophin is a protein that is found in the sarcolemma facing the sarcoplasm. It functions as a cytoskeletal integrator giving the membrane stability. It protects the muscle cells from contraction-induced damage. Genetic mutations of the dystrophin complex cause muscular weakness and muscular dystrophy.
Myasthenia gravis is another disease that affects the sarcolemma. This is an autoimmune disease whereby autoantibodies are directed towards the nAChRs on the sarcolemma. These antibodies can block or destroy these receptors. This leads to muscle weakness, shortness of breath, vision problems, difficulty swallowing, and drooping of the eyelids.
Biological Importance of Sarcolemma
Biologically, the sarcolemma has many functions and is more than just a cell membrane. As well as allowing endo- and exocytosis, the sarcolemma acts as a barrier and a link to the cytoskeleton of the extracellular matrix. It is also an electrical insulator.
As a neuromuscular junction, it functions to propagate action potentials and is involved in excitation-contraction coupling. Furthermore, calcium influx through the sarcolemma allows it to repair and continue to maintain a barrier function. If the membrane is damaged, calcium enters which triggers vesicle exocytosis and vesicle fusion leading to the formation of a patch at the site of injury (membrane patch). Figure 8 shows this process. Abnormal calcium flow can lead to problems with muscle fiber function. It causes changes in ion regulation in muscle proteins. It is thought that incorrect calcium flow may be involved in muscle fiber degradation in muscular dystrophy.
The importance of the sarcolemma as a biological entity is highlighted by diseases that cause its dysfunction.
- Al-Qusairi, L., Laporte, J.(2011). T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases. Skeletal Muscle 1, 26 . https://doi.org/10.1186/2044-5040-1-26
- Biga, L.M et al. Anatomy and Physiology – Skeletal Muscle. Oregon State University. https://open.oregonstate.education/aandp/chapter/10-2-skeletal-muscle/
- Calderón, J. C., Bolaños, P., & Caputo, C. (2014). The Excitation-Contraction Coupling Mechanism in Skeletal Muscle. Biophysical reviews, 6(1), 133–160. https://doi.org/10.1007/s12551-013-0135-x
- Definition of Sarcolemma. Histology@yale. http://medcell.med.yale.edu/cgi-bin/keyword.cgi?keyword=sarcolemma
- Difference Between A-band and I-band of Sacromere, Comparison Tab. Easy Biology Class. https://www.easybiologyclass.com/difference-between-a-band-and-i-band-of-sarcomere-comparison-tab/
- Gao, Q. Q., & McNally, E. M. (2015). The Dystrophin Complex: Structure, Function, and Implications for Therapy. Comprehensive Physiology, 5(3), 1223–1239. https://doi.org/10.1002/cphy.c140048
- Katzemich, A., Kreisköther, N., Alexandrovich, A., Elliott, C., Schöck, F., Leonard, K., Sparrow, J., & Bullard, B. (2012). The function of the M-line protein obscurin in controlling the symmetry of the sarcomere in the flight muscle of Drosophila. Journal of cell science, 125(Pt 14), 3367–3379. https://doi.org/10.1242/jcs.097345
- Monne, H., et al. (2013). Structure of glycocalyx. BioPhysical Journal. (104)2. Supplement 1, 251a. https://doi.org/10.1016/j.bpj.2012.11.1412
- Ohlendieck K. (2000-2013) The Pathophysiological Role of Impaired Calcium Handling in Muscular Dystrophy. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; https://www.ncbi.nlm.nih.gov/books/NBK6173/
- Office of Communications and Public Liaison. (2020). Myasthenia Gravis Fact Sheet. National institute of neurological disorders and stroke. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet
- Rivero, J. L., Piercy, R. J. (2008). Chapter 2.1. Muscle Physiology, Responses to Exercise and Training. Equine Exercise Physiology. (2.1) 30 – 80.
- Valberg, S.J. (2008). Skeletal Muscle Function. Clinical biochemistry of domestic animals sixth Edition. (15) 459-484.
- Weisleder, N. Sarcolemma in health a disease. Department of Physiology and Cell Biology Davis Heart and Lung Research Institute. The Ohio State University. www.nationwidechildrens.org.
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