The Neuromuscular Junction
Another specialization of the skeletal muscle is the site where a motor neuron’s terminal meets the muscle fiber—called the neuromuscular junction (NMJ). This is where the muscle fiber first responds to signaling by the motor neuron. Every skeletal muscle fiber in every skeletal muscle is innervated by a motor neuron at the NMJ. Excitation signals from the neuron are the only way to functionally activate the fiber to contract.
Every skeletal muscle fiber is supplied by a motor neuron at the NMJ. Watch this video to learn more about what happens at the NMJ. (a) What is the definition of a motor unit? (b) What is the structural and functional difference between a large motor unit and a small motor unit? (c) Can you give an example of each? (d) Why is the neurotransmitter acetylcholine degraded after binding to its receptor?
All living cells have membrane potentials, or electrical gradients across their membranes. The inside of the membrane is usually around -60 to -90 mV, relative to the outside. This is referred to as a cell’s membrane potential. Neurons and muscle cells can use their membrane potentials to generate electrical signals. They do this by controlling the movement of charged particles, called ions, across their membranes to create electrical currents. This is achieved by opening and closing specialized proteins in the membrane called ion channels. Although the currents generated by ions moving through these channel proteins are very small, they form the basis of both neural signaling and muscle contraction.
Both neurons and skeletal muscle cells are electrically excitable, meaning that they are able to generate action potentials. An action potential is a special type of electrical signal that can travel along a cell membrane as a wave. This allows a signal to be transmitted quickly and faithfully over long distances.
Although the term excitation-contraction coupling confuses or scares some students, it comes down to this: for a skeletal muscle fiber to contract, its membrane must first be “excited”—in other words, it must be stimulated to fire an action potential. The muscle fiber action potential, which sweeps along the sarcolemma as a wave, is “coupled” to the actual contraction through the release of calcium ions (Ca++) from the SR. Once released, the Ca++ interacts with the shielding proteins, forcing them to move aside so that the actin-binding sites are available for attachment by myosin heads. The myosin then pulls the actin filaments toward the center, shortening the muscle fiber.
In skeletal muscle, this sequence begins with signals from the somatic motor division of the nervous system. In other words, the “excitation” step in skeletal muscles is always triggered by signaling from the nervous system (Figure 10.2.4).
The motor neurons that tell the skeletal muscle fibers to contract originate in the spinal cord, with a smaller number located in the brainstem for activation of skeletal muscles of the face, head, and neck. These neurons have long processes, called axons, which are specialized to transmit action potentials long distances— in this case, all the way from the spinal cord to the muscle itself (which may be up to three feet away). The axons of multiple neurons bundle together to form nerves, like wires bundled together in a cable.
Signaling begins when a neuronal action potential travels along the axon of a motor neuron, and then along the individual branches to terminate at the NMJ. At the NMJ, the axon terminal releases a chemical messenger, or neurotransmitter, called acetylcholine (ACh). The ACh molecules diffuse across a minute space called the synaptic cleft and bind to ACh receptors located within the motor end-plate of the sarcolemma on the other side of the synapse. Once ACh binds, a channel in the ACh receptor opens and positively charged ions can pass through into the muscle fiber, causing it to depolarize, meaning that the membrane potential of the muscle fiber becomes less negative (closer to zero.)
As the membrane depolarizes, another set of ion channels called voltage-gated sodium channels are triggered to open. Sodium ions enter the muscle fiber, and an action potential rapidly spreads (or “fires”) along the entire membrane to initiate excitation-contraction coupling.
Things happen very quickly in the world of excitable membranes (just think about how quickly you can snap your fingers as soon as you decide to do it). Immediately following depolarization of the membrane, it repolarizes, re-establishing the negative membrane potential. Meanwhile, the ACh in the synaptic cleft is degraded by the enzyme acetylcholinesterase (AChE) so that the ACh cannot rebind to a receptor and reopen its channel, which would cause unwanted extended muscle excitation and contraction.
Propagation of an action potential along the sarcolemma is the excitation portion of excitation-contraction coupling. Recall that this excitation actually triggers the release of calcium ions (Ca++) from its storage in the cell’s SR. For the action potential to reach the membrane of the SR, there are periodic invaginations in the sarcolemma, called T-tubules (“T” stands for “transverse”). You will recall that the diameter of a muscle fiber can be up to 100 μm, so these T-tubules ensure that the membrane can get close to the SR in the sarcoplasm. The arrangement of a T-tubule with the membranes of SR on either side is called a triad (Figure 10.2.5). The triad surrounds the cylindrical structure called a myofibril, which contains actin and myosin.
The T-tubules carry the action potential into the interior of the cell, which triggers the opening of calcium channels in the membrane of the adjacent SR, causing Ca++ to diffuse out of the SR and into the sarcoplasm. It is the arrival of Ca++ in the sarcoplasm that initiates contraction of the muscle fiber by its contractile units, or sarcomeres.
Skeletal muscles contain connective tissue, blood vessels, and nerves. There are three layers of connective tissue: epimysium, perimysium, and endomysium. Skeletal muscle fibers are organized into groups called fascicles. Blood vessels and nerves enter the connective tissue and branch in the cell. Muscles attach to bones directly or through tendons or aponeuroses. Skeletal muscles maintain posture, stabilize bones and joints, control internal movement, and generate heat.
Skeletal muscle fibers are long, multinucleated cells. The membrane of the cell is the sarcolemma; the cytoplasm of the cell is the sarcoplasm. The sarcoplasmic reticulum (SR) is a form of endoplasmic reticulum. Muscle fibers are composed of myofibrils. The striations are created by the organization of actin and myosin resulting in the banding pattern of myofibrils.
Interactive Link Questions
Watch this video to learn more about macro- and microstructures of skeletal muscles. (a) What are the names of the “junction points” between sarcomeres? (b) What are the names of the “subunits” within the myofibrils that run the length of skeletal muscle fibers? (c) What is the “double strand of pearls” described in the video? (d) What gives a skeletal muscle fiber its striated appearance?
Answer: (a) Z-lines. (b) Sarcomeres. (c) This is the arrangement of the actin and myosin filaments in a sarcomere. (d) The alternating strands of actin and myosin filaments.
Every skeletal muscle fiber is supplied by a motor neuron at the NMJ. Watch this video to learn more about what happens at the neuromuscular junction. (a) What is the definition of a motor unit? (b) What is the structural and functional difference between a large motor unit and a small motor unit? Can you give an example of each? (c) Why is the neurotransmitter acetylcholine degraded after binding to its receptor?
Answer: (a) It is the number of skeletal muscle fibers supplied by a single motor neuron. (b) A large motor unit has one neuron supplying many skeletal muscle fibers for gross movements, like the Temporalis muscle, where 1000 fibers are supplied by one neuron. A small motor has one neuron supplying few skeletal muscle fibers for very fine movements, like the extraocular eye muscles, where six fibers are supplied by one neuron. (c) To avoid prolongation of muscle contraction.
Q. The correct order for the smallest to the largest unit of organization in muscle tissue is ________.
A. fascicle, filament, muscle fiber, myofibril
B. filament, myofibril, muscle fiber, fascicle
C. muscle fiber, fascicle, filament, myofibril
D. myofibril, muscle fiber, filament, fascicle
Q. Depolarization of the sarcolemma means ________.
A. the inside of the membrane has become less negative as sodium ions accumulate
B. the outside of the membrane has become less negative as sodium ions accumulate
C. the inside of the membrane has become more negative as sodium ions accumulate
D. the sarcolemma has completely lost any electrical charge
Critical Thinking Questions
Q. What would happen to skeletal muscle if the epimysium were destroyed?
A. Muscles would lose their integrity during powerful movements, resulting in muscle damage.
Q. Describe how tendons facilitate body movement.
A. When a muscle contracts, the force of movement is transmitted through the tendon, which pulls on the bone to produce skeletal movement.
Q. What are the five primary functions of skeletal muscle?
A. Produce movement of the skeleton, maintain posture and body position, support soft tissues, encircle openings of the digestive, urinary, and other tracts, and maintain body temperature.
Q. What are the opposite roles of voltage-gated sodium channels and voltage-gated potassium channels?
A. The opening of voltage-gated sodium channels, followed by the influx of Na+, transmits an Action Potential after the membrane has sufficiently depolarized. The delayed opening of potassium channels allows K+ to exit the cell, to repolarize the membrane.
- acetylcholine (ACh)
- neurotransmitter that binds at a motor end-plate to trigger depolarization
- protein that makes up most of the thin myofilaments in a sarcomere muscle fiber
- action potential
- change in voltage of a cell membrane in response to a stimulus that results in transmission of an electrical signal; unique to neurons and muscle fibers
- broad, tendon-like sheet of connective tissue that attaches a skeletal muscle to another skeletal muscle or to a bone
- to reduce the voltage difference between the inside and outside of a cell’s plasma membrane (the sarcolemma for a muscle fiber), making the inside less negative than at rest
- loose, and well-hydrated connective tissue covering each muscle fiber in a skeletal muscle
- outer layer of connective tissue around a skeletal muscle
- excitation-contraction coupling
- sequence of events from motor neuron signaling to a skeletal muscle fiber to contraction of the fiber’s sarcomeres
- bundle of muscle fibers within a skeletal muscle
- motor end-plate
- sarcolemma of muscle fiber at the neuromuscular junction, with receptors for the neurotransmitter acetylcholine
- long, cylindrical organelle that runs parallel within the muscle fiber and contains the sarcomeres
- protein that makes up most of the thick cylindrical myofilament within a sarcomere muscle fiber
- neuromuscular junction (NMJ)
- synapse between the axon terminal of a motor neuron and the section of the membrane of a muscle fiber with receptors for the acetylcholine released by the terminal
- signaling chemical released by nerve terminals that bind to and activate receptors on target cells
- connective tissue that bundles skeletal muscle fibers into fascicles within a skeletal muscle
- longitudinally, repeating functional unit of skeletal muscle, with all of the contractile and associated proteins involved in contraction
- plasma membrane of a skeletal muscle fiber
- cytoplasm of a muscle cell
- sarcoplasmic reticulum (SR)
- specialized smooth endoplasmic reticulum, which stores, releases, and retrieves Ca++
- synaptic cleft
- space between a nerve (axon) terminal and a motor end-plate
- projection of the sarcolemma into the interior of the cell
- thick filament
- the thick myosin strands and their multiple heads projecting from the center of the sarcomere toward, but not all to way to, the Z-discs
- thin filament
- thin strands of actin and its troponin-tropomyosin complex projecting from the Z-discs toward the center of the sarcomere
- the grouping of one T-tubule and two terminal cisternae
- regulatory protein that binds to actin, tropomyosin, and calcium
- regulatory protein that covers myosin-binding sites to prevent actin from binding to myosin
- voltage-gated sodium channels
- membrane proteins that open sodium channels in response to a sufficient voltage change, and initiate and transmit the action potential as Na+ enters through the channel