Learn high-yield musculoskeletal system concepts for the MCAT, including anatomy, physiology, and common traps, with practice questions.
(Note: This guide is part of our MCAT Biology series.)
Table of Contents
Part 1: Introduction
Part 2: Types of muscle
a) Skeletal muscle
b) Smooth muscle
c) Cardiac muscle
Part 3: Muscle Contraction
Part 4: Additional Connective Elements
a) Bone structure
b) Bone maintenance
c) Tendons, ligaments, and cartilage
Part 5: Skin
a) Structure
b) Homeostasis
Part 6: High-Yield Terms
Part 7: Passage-Based Questions and Answers
Part 8: Standalone Questions and Answers
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Part 1: Introduction
The musculoskeletal system supports the body and allows us to move. Therefore, it is important to understand its structure as well as how muscle contraction typically occurs.
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Part 2: Types of muscle
There are many different types of muscle throughout the body, and all types have various forms and functions. In this section, we will introduce you to three different types of muscle: skeletal, cardiac, and smooth muscle.
Skeletal muscle is the tissue responsible for voluntary movement. It is consciously controlled and innervated by the somatic nervous system innervations (more to follow in part three). Skeletal muscles are striated, or striped, and are multinucleated.
There are two types of skeletal muscle fibers: slow-twitch fibers and fast-twitch fibers. These two forms of muscle differ in their contractile velocity, or how rapidly they are capable of contracting to produce movement. Slow-twitch fibers are sometimes referred to as red fibers or type I fibers and have low contractile velocity. They are red because they carry lots of myoglobin, an oxygen carrier that only has one subunit of hemoglobin. Slow-twitch fibers also have large amounts of mitochondria and are slower to fatigue. Fast-twitch fibers are also called white fibers or type II fibers and have high contractile velocity. They contain much less myoglobin and are therefore lighter in color. They contract rapidly but tire quickly.
Skeletal muscles are additionally prone to suffering fatigue. Fatigue is a consequence of suffering oxygen debt: a disparity between how much oxygen the muscles require to produce sufficient energy (in the form of ATP), and how much oxygen is being provided through breathing. (For more information on the role of oxygen in energy production, be sure to refer to our guide on carbohydrate metabolism.)
The contraction and relaxation of skeletal muscle around the body perform an additional function in moving fluids. Blood and lymph, residing in blood vessels and lymph vessels, may be periodically “squeezed” due to the motion of the surrounding skeletal muscles. This movement assists in returning fluid from the periphery of the body, where blood pressure tends to be low.
A sarcomere is a unit of skeletal muscle. Sarcomeres are composed of two different strands of protein filaments colloquially called thick and thin filaments. These filaments interweave with each other in what is referred to as the contractile apparatus. Thick filaments are composed of myosin, while thin filaments are made of actin. Troponin and tropomyosin attach to the actin, which works together with myosin to contract muscle. Sarcomeres are connected end-to-end to form myofibrils. Each myofibril is surrounded by sarcoplasmic reticulum, a specialized membranous organelle that contains high concentrations of Ca²⁺ ions. These Ca²⁺ ions play an important role in muscle contraction.
Smooth muscle is involuntary and is controlled and innervated by the autonomic nervous system. Smooth muscle lines the digestive tract, bladder, uterus, blood vessel walls, and other regions of the body responsible for transportation of material or peristalsis. Both skeletal and smooth muscles are made of thick and thin filaments. Both skeletal and smooth muscles respond to input from the nervous system to undergo contraction. However, in smooth muscle, the myosin and actin fibers are not organized into sarcomeres. Additionally, smooth muscle can exhibit myogenic activity, which is contraction without nervous system input, and has led to the common belief that there is a “second brain” in your gut! In addition, smooth muscles are not striated and only have a single nucleus at the cell center.
Cardiac muscle is unique to the heart and contains characteristics of both skeletal and smooth muscle. Like skeletal muscle, cardiac muscle is striated and composed of sarcomeres. Like smooth muscle, cardiac muscle is involuntary, and each muscle cell only contains one nucleus. Cardiac muscle cells are separated by intercalated discs. These intercalated discs contain many gap junctions that allow for ions to rapidly flow and action potentials to be quickly propagated throughout the heart, resulting in efficient and coordinated contraction. While action potentials in neurons require the propagation of signals through one nerve cell at a time, the unhindered flow of calcium ions through gap junctions allows for synchronized contraction.
Cardiac muscle cells exhibit myogenic activity, or electrical activity independent of the brain that regulates the rhythm of the heart. These electrical signals start at a cluster of specialized electrical cells at the top of the heart, known as the sinoatrial node. The electrical signals then propagate throughout the heart, triggering muscle contraction. From the sinoatrial (SA) node, the signal travels through the atrioventricular (AV) node and the Bundle of His. Lastly, the signal spreads through the Purkinje fibers: branching fibers in the walls of the heart ventricles that induce contraction in the cardiac muscle.
Figure 1 A depiction of the flow of electricity through the heart.
Table 1 Summary table of the three types of muscle
| Skeletal | Smooth | Cardiac |
|---|---|---|
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Part 3: Muscle contraction
Recall that the muscle fibers contain both thick and thin filaments, which are also known as actin and myosin. In skeletal muscle, interactions between actin and myosin will ultimately shorten muscles to move the body. This process happens through a special cycle known as the actin-myosin crossbridge cycle.
Before this cycle can take place, a signal must be sent from the somatic nervous system. After signals from the brain are propagated through motor neurons, the signal will arrive at the junction between the nerve terminal and the muscle fiber. The nerve terminal makes contact at the motor endplate of the neuromuscular junction.
At the neuromuscular junction, the nervous system’s motor neurons interact with muscles through a chemical synapse. When an axon in the somatic nervous system is activated, an action potential will travel down to the axon terminal and release acetylcholine into the synaptic cleft. The acetylcholine then binds to the sarcolemma of the receiving muscle cell, opening ion channels in the cell membrane. The influx of ions will depolarize the cell membrane and create another action potential. This action potential moves through structures called T-tubules, which are long invaginations in the cell membrane of the muscle cell. These long invaginations increase the amount of surface area in contact with the sarcoplasmic reticulum, increasing the speed of signal propagation and stimulating the sarcoplasmic reticulum to release the Ca²⁺ ions that it stores.
Figure 2 Action potential propagation at the neuromuscular junction. (1) Action potential travels down the axon, releasing acetylcholine into the synaptic cleft. (2) Acetylcholine binds to the sarcolemma, opening ion channels and propagating an action potential through T-tubules.
Figure 3 Ca2+ ions help in initiating the actin-myosin crossbridge cycle.
Actin and myosin in muscle cells at rest are usually bound to tropomyosin and troponin, additional large proteins that are present in the cell. In the resting noncontractile state of the muscle cell, tropomyosin covers the myosin-binding sites in actin. However, the Ca²⁺ released by the sarcoplasmic reticulum binds to troponin. This leads to a conformational change in tropomyosin that exposes the myosin binding site in actin. In other words, the presence of Ca²⁺ allows the actin-myosin crossbridge to form.
Once these binding sites are exposed, the myosin head releases ADP and inorganic phosphate (Pi)—resulting from the cleavage of ATP—providing the energy that results in the power stroke. The power stroke allows the myosin to “pull” itself along the actin filament. While each power stroke is relatively short and incremental, the repeated action of thousands of myosin heads ultimately results in a shortening of the sarcomere!
After the power stroke, ATP from the cytoplasm binds to the myosin head, releasing it from actin. Tropomyosin immediately recovers the binding site. Once ATP is bound, it is hydrolyzed into ADP and Pi, allowing the myosin head to cock back into its initial high-energy position, and for the cycle to begin again.
Figure 4 The actin-myosin crossbridge cycle. (1) Resting state; myosin is already cocked back in high-energy position. (2) Ca2+ binds to troponin, exposing the binding site. (3) Power stroke; contraction. ADP + Pi dissociate. (4) New ATP binds to myosin. Myosin detaches from actin, Ca2+ detaches from troponin. (5) Hydrolysis of ATP; resetting of myosin head.
It’s important to note that muscles throughout the body are under the control of multiple components of the nervous system. Voluntary movements performed by most skeletal muscles are under the control of the somatic nervous system. Involuntary movements performed by most cardiac and smooth muscles are under the control of the autonomic nervous system. These involuntary movements include muscular activity such as shivering. Shivering is the result of small contractile movements performed by skeletal muscles, which create heat through energy expenditure and assist in thermoregulation.
Since the autonomic nervous system oversees both the sympathetic and parasympathetic responses, the innervated muscle can engage in opposing behaviors. When the sympathetic response (e.g., “fight or flight”) is activated, smooth muscle lining the blood vessels is stimulated to dilate while the digestive tract is slowed. When the parasympathetic response (e.g., “rest and digest”) is activated, the converse occurs.
For more information on this, be sure to refer to our guide on the nervous system.
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Part 4: Additional connective elements
While muscles are an important component of our soft tissue, we need additional structural elements to give our bodies shape and provide leverage for movement. This structure comes from bones within our body and the attachments at which muscles connect.
Since the human skeleton is located within the body, it is referred to as an endoskeleton. This is in contrast to structural elements located externally to an organism’s body, which is referred to as an exoskeleton.
a) Bone structure
Contrary to its appearance, bone is a dynamic living tissue that is both vascular and innervated. Beyond the protection of soft tissues and support of movement, bones have the valuable function of storing fat and minerals and producing red blood cells.
Long bones, such as the bones in our arms and legs, are characterized by a cylindrical shaft called the diaphysis, and wider ends called the epiphyses. These epiphyses are composed of a material called spongy bone, which contains red bone marrow. Despite its name, spongy bone is quite rigid. The pockets within spongy bone provide spaces for the storage of bone marrow.
There are two types of bone marrow: red marrow and yellow marrow. Red bone marrow is typically found in spongy bone and is the site of hematopoiesis, or red blood cell development. Yellow bone marrow is typically found in the cavity of the diaphysis and stores adipose (i.e., fat).
Figure 5 Anatomy of a long bone.
Compact bone has a unique, organized microscopic structure. Its strength comes from the bone matrix, which is made of units called osteons. These osteons are units of bone structure that are interwoven with systems of canals. Haversian canals run through the center of each osteon, along the length of the bone. Each Haversian canal is surrounded by concentric rings of bone matrix called lamellae. Haversian canals are perpendicularly connected through Volkmann’s canals. Each of these canals contains blood vessels and sometimes nerve endings.
Although the lamellae are concentric rings, they are interspersed throughout the compact bone and do not fuse to form a perfectly solid material. The spaces between lamellae are called lacunae. These lacunae store osteocytes, or mature bone cells.
Figure 6 A view of the systems within bone matrix.
b) Bone maintenance
Bones are continuously torn down and built back up to maintain mineral homeostasis in our blood. In fact, most of the body’s Ca²⁺ is stored in a mineral known as hydroxyapatite in the bone matrix. In order to maintain proper Ca²⁺ levels in our bloodstream, we need cells to both destroy bone and rebuild it. Two types of bone cells serve this function: osteoclasts and osteoblasts. Osteoclasts resorb bone matrix and release minerals back into the blood, while osteoblasts reform and grow bones. (Think: osteoblasts build bone; osteoclasts consume bone).
The activity of osteoblasts and osteoclasts is regulated by the peptide hormones calcitonin and parathyroid hormone. Calcitonin is secreted by the thyroid gland, while parathyroid hormone (PTH) is secreted by the parathyroid glands. If blood calcium levels are too high, the thyroid releases calcitonin. Calcitonin stimulates osteoblasts to build up bones, resorbing Ca²⁺ from the bloodstream and locking it away. If blood Ca²⁺ levels are too low, the parathyroid releases PTH, which stimulates osteoclasts to consume bone and release Ca²⁺ back into the bloodstream. The thyroid and parathyroid glands work closely with the urinary system to maintain proper calcium levels within the body.
Figure 7 Endocrine regulation of calcium.
c) Tendons, ligaments, and cartilage
Tendons, ligaments, and cartilage serve as points of attachment between bone and muscle. Tendons connect muscles to bones, while ligaments directly connect bone to bone. Both tendons and ligaments are primarily composed of strong, flexible connective tissue known as collagen.
Cartilage is a strong, flexible connective tissue composed of a collagen matrix called chondrin. The most common type of cartilage is hyaline cartilage, which reduces friction and absorbs shock between joints. In early human life, the skeleton is primarily composed of cartilage, allowing for the rapid growth of the brain and other organs. Over time, the material is slowly replaced by hardened bone.
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Part 5: Skin
a) Structure
The skin is the largest organ in the body and arises from the ectoderm. It is divided into three layers: the epidermis, the dermis, and the hypodermis.
The epidermis is the uppermost layer and is divided into 5 strata, or layers. The epidermis also contains key cell types you should know for test day.
Keratinocytes produce keratin, a protein that serves to protect the skin from pathogens and injuries
Melanocytes produce the pigment melanin, which protects the skin from UV radiation
Langerhans cells are a type of macrophage that assists in immune system activation
The different strata of the epidermis are summarized in the table below.
Table 2 The layers of skin
| Layer of epidermis | Key features |
|---|---|
| • Contains flattened keratin producing cells, keratinocytes, to protect against pathogens | |
| • Found in hairless skin (e.g., palms) | |
| • Contains dead keratinocytes | |
| • Contains Langerhans cells • Contains live keratinocytes |
|
| • Site of proliferation for keratinocytes • Contains melanocytes • Contains stem cells |
The dermis contains sweat glands, hair follicles, and blood vessels. Also present are nerve endings that provide sensory information.
Tactile corpuscles, also known as Meissner’s corpuscles, are mechanoreceptors that respond to light touch
Bulbous corpuscles, also known as Ruffini endings, are mechanoreceptors that respond to the stretching of the skin
Pacinian corpuscles are mechanoreceptors that respond to vibration and pressure
For more information on how this sensory information is processed, be sure to refer to our guide on consciousness, sensation, and perception.
The hypodermis is the bottom layer of the skin. It is a connective tissue that connects the skin to the body’s muscles and bones. It contains adipose tissue to store fat and provide thermal insulation. Additionally, it provides protection by absorbing shock impacts to the skin.
b) Homeostasis
The skin plays a crucial role in maintaining homeostasis. First, due to its impermeability to water, the skin allows the body to maintain its osmolarity. Moreover, it contains a variety of structures and mechanisms responsible for thermoregulation.
During shivering, the rapid contraction of skeletal muscles results in the conversion of mechanical energy into thermal energy. The process of piloerection, or goosebumps, results in the raising of hairs of the skin to trap heat in the layer of air immediately surrounding the body. Finally, the body also uses vasoconstriction, or the constriction of blood vessels, to retain heat when under cold conditions.
Under warm conditions, the body uses sweat to cool itself. Sweat glands secrete this mixture of water and ions onto the skin. In this process of evaporative cooling, heat is lost and thus cooling down the body. This is often coupled with vasodilation, or the widening of blood vessels. By bringing warm blood to the surface of the skin, the heat from the blood can be released into the cooler ambient air, thus allowing the body to release heat and cool down.
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Part 6: High-yield terms
Skeletal muscle: tissue responsible for voluntary movement; consciously controlled and innervated by the somatic nervous system innervations
Sarcomere: a unit of skeletal muscle, composed of actin and myosin
Sarcoplasmic reticulum: a specialized membranous organelle in the sarcomere that contains high concentrations of Ca²⁺ ions
Smooth muscle: involuntary muscle; controlled and innervated by the autonomic nervous system
Cardiac muscle: muscle found in the heart; contains intercalated discs and may be multinucleated
Myogenic activity: electrical activity independent of the brain that regulates the rhythm of the heart
Actin-myosin crossbridge cycle: a 4-step cycle of ATP cleavage and actin-myosin binding that ultimately results in muscle contraction
Neuromuscular junction: where the nervous system’s motor neurons interact with muscles through a chemical synapse
Red bone marrow: typically found in spongy bone, and is the site of hematopoiesis, or red blood cell development
Yellow bone marrow: typically found in the cavity of the diaphysis, and stores adipose (i.e., fat)
Haversian canals: longitudinal canals through the center of osteons; contain blood vessels
Osteoclasts: bone cells that resorb bone matrix and release minerals back into the blood; stimulated by parathyroid hormone
Osteoblasts: bone cells that reform and grow bones; stimulated by calcitonin
Tendons: connect muscles to bones; formed by collagen
Ligaments: connect bone to bone; formed by collagen
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Part 7: Passage-based questions and answers
Osteoclasts play an important role in bone resorption with respect to bone development and calcium homeostasis. Dysfunction of osteoclasts leads to bone loss in many skeletal diseases, such as rheumatoid arthritis and periodontitis. Osteoclasts may also play a role in immune-related diseases and certain inflammatory processes as they are closely related to macrophages of the immune system. Therefore, understanding the process of osteoclasts differentiation and formation is important for illuminating bone disease mechanisms.
G-proteins, also known as guanine nucleotide-binding proteins, are coupled with specific receptors to mediate signaling pathways that contribute to cellular activities such as cell growth and differentiation. In particular, Gα13 is a member of the G12 subfamily of G-proteins. Gα13 is already known to play important roles in many biological processes, including embryogenesis, angiogenesis, cell transformation, and metastatic tumor progression. It also helps regulate different signaling pathways, including the MAPK pathway and Rho GTPases. However, scientists have discovered a new role of G-protein Gα13 in the regulation of osteoclast function. In a new study, Gα13 was highly expressed in multinucleated osteoclasts, suggesting that Gα13 had a functional role in mature osteoclasts. More specifically, researchers suggest that Gα13 inhibits osteoclast cytoskeleton organization to create a negative feedback mechanism.
In the study, the researchers knocked out Gα13 expression in osteoclast precursors in mice, which is a genotype referred to as Gα13ΔM/ΔM. They subjected the femur bones of the mice to tartrate-resistant acid phosphatase (TRAP) staining to visualize and quantify the osteoclasts present. Meanwhile, micro-computed tomography (µCT) analysis was performed to evaluate bone volume and structure. Their results are shown in the figure below:
Figure 1 Oc.N/B.pm, number of osteoclasts per bone perimeter; Oc.N/BS, osteoclast surface per bone surface; OC size, osteoclast surface divided by osteoclast number. All data are shown as mean ± S.D. ***p<0.001, n.s., not statistically significant
Question 1: Based on the information presented in the passage, the presence of a Gα13 agonist would most likely lead to:
A) Increase in osteoclasts and increase in blood calcium levels
B) Increase in osteoclasts and decrease in blood calcium levels
C) Decrease in osteoclasts and increase in blood calcium levels
D) Decrease in osteoclasts and decrease in blood calcium levels
Question 2: Which of the following hormones will most likely stimulate the production of Gα13?
A) Testosterone
B) Estrogen
C) PTH
D) Calcitonin
Question 3: Based on the results shown in figure 1, which of the following conclusions can be drawn about the role of Gα13?
A) The presence of Gα13 increases osteoclast size but not osteoclast numbers.
B) The presence of Gα13 decreases osteoclast size but not osteoclast numbers.
C) The presence of Gα13 decreases osteoclast size and decreases osteoclast numbers.
D) Not enough information is presented to be able to draw a conclusion.
Question 4: Scientists took the femurs and tibia of Gα13ΔM/ΔM mice and analyzed their bone phenotypes. Which of the following phenotypes of Gα13ΔM/ΔM mice would the scientists most likely have predicted?
A) Decreased bone mineral density, decreased bone volume, decreased osteoclast surface
B) Decreased bone mineral density, decreased bone volume, increased osteoclast surface
C) Increased bone mineral density, increased bone volume, decreased osteoclast surface
D) Decreased bone mineral density, increased bone volume, increased osteoclast surface
Answer key for passage-based questions
1. Answer choice D is correct. An agonist is a molecule that binds to a receptor and produces the corresponding cell response. According to the passage, Gα13 negatively inhibits osteoclasts. Therefore, the presence of a Gα13 agonist would decrease osteoclast levels (choices A and B are incorrect). A decrease in osteoclasts would lead to lower blood calcium levels (choice D is correct).
2. Answer choice C is correct. Testosterone and estrogen are sex hormones that do not directly regulate calcium levels (choices A and B are incorrect). Increasing Gα13 indicates an increase in osteoclasts. PTH stimulates osteoclasts, while calcitonin stimulates osteoblasts. Therefore, an increase in PTH could lead to an increase in the number of osteoclasts, resulting in the stimulation of Gα13 (choice C is correct).
3. Answer choice B is correct. The graph on the left represents the number of osteoclasts per bone perimeter. In this graph, WT mice and Gα13ΔM/ΔM osteoclasts numbers are not statistically significant (i.e., the error bars overlap). Thus, the presence of Gα13 does not change osteoclast numbers (choices C and D are incorrect). The middle graph shows the percent of osteoclast surface on the bone, and the right graph shows osteoclast size. Both graphs indicate that in Gα13ΔM/ΔM mice, osteoclast size increases (choice A is incorrect). In other words, the presence of Gα13 decreases osteoclast size (choice B is correct).
4. Answer choice B is correct. A Gα13ΔM/ΔM knockout mouse should be unable to negatively inhibit osteoclast function. Therefore, osteoclasts levels are uncontrollably elevated in Gα13ΔM/ΔM knockout mice, suggesting an increase in osteoclast surface (choices A and C are incorrect). Osteoclasts consume bone. Elevated osteoclast levels would therefore lead to decreased mineral bone density and decreased bone volume (choice B is correct).
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Part 8: Standalone questions and answers
Question 1: Which of the following statements is false?
A) Cardiac muscle is striated
B) Ca²⁺ is required for cardiac muscle to contract
C) Cardiac muscle cells are multinucleated
D) Depolarization of cardiac muscle cells starts from the SA node
Question 2: An increase of blood calcitonin would most likely stimulate the production of which of the following cells?
A) Osteoblasts
B) Osteoclasts
C) Osteocytes
D) Osteons
Question 3: Which of the following is NOT a function of bone?
A) Production of red blood cells
B) Blood filtration
C) Energy storage
D) Hematopoiesis
Question 4: Scientists have recently discovered a drug that inhibits PTH. Which of the following is most likely to be an effect of the drug?
A) Decrease in osteoclasts and decrease in bone hydroxyapatite levels
B) Decrease in osteoclasts and increase in bone hydroxyapatite levels
C) Decrease in osteoblasts and decrease in bone hydroxyapatite levels
D) Decrease in osteoblasts and increase in bone hydroxyapatite levels
Question 5: Which of the following statements is false?
A) Smooth muscle is involuntary
B) Smooth muscles can be found in the bladder and blood vessels
C) Smooth muscle requires calcium to contract
D) Smooth muscles cannot exhibit myogenic activity
Answer key for standalone questions
1. Answer choice C is correct. Cardiac muscle appears striated, similarly to skeletal muscle (choice A is incorrect). All muscles require the presence of Ca²⁺ to contract (choice B is incorrect). The sinoatrial node, or SA node, is the “pacemaker” of the heart and initiates electrical activity to induce contraction of the heart (choice D is incorrect). While skeletal muscle cells are typically multinucleated, most cardiac muscle cells are mononucleated and occasionally possess two nuclei (choice C is correct).
2. Answer choice A is correct. Calcitonin stimulates osteoblasts to build up bones in response to high blood Ca²⁺ levels. Osteoclasts consume bone and are stimulated by PTH (choice B is incorrect). Osteocytes are mature bone cells found in lacunae (choice C is incorrect). Osteons are bone matrix units found in long bones (choice D is incorrect).
3. Answer choice B is correct. Blood filtration is the primary function of kidneys (choice B is correct). Hematopoiesis, or red blood cell development, takes place in spongy bone (choices A and D are incorrect). Yellow bone marrow in the medullary cavity of the diaphysis stores energy in the form of adipose tissue (choice C is incorrect).
4. Answer choice B is correct. PTH stimulates osteoclasts, which consume bone. Therefore, inhibiting PTH would decrease osteoclasts (choices C and D are incorrect). Hydroxyapatite is the form in which Ca²⁺ is stored in bones. Without osteoclasts, Ca²⁺ would remain in the bone, increasing hydroxyapatite levels (choice A is incorrect).
5. Answer choice D is correct. Smooth muscles can exhibit myogenic activity, which refers to contraction without stimulation from the nervous system (choice D is correct). Smooth muscle is found in the digestive tract, bladder, and blood vessels—all parts of the body innervated by the autonomic nervous system (choices A and B are incorrect). All muscles need calcium to contract (choice C is incorrect).
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