Summary

Vertebrate Skeletal Muscle Cells

• Each whole muscle consists of bundles of longitudinally arrayed muscle fibers, which in turn consist of longitudinally arranged myofibrils made up of thick (myosin) and thin (actin) myofilaments organized into sarcomeres.
• A single myofibril consists of a longitudinal series of sarcomeres. The myofibrils are aligned in register in a muscle fiber so that they give the fiber a striped, or striated, appearance. Titin, nebulin, and obscurin are giant proteins that maintain the internal structural organization of the muscle fiber.
• The contractile proteins actin and myosin polymerize in a polarized fashion to form the thin and thick filaments. During contraction, the heads of individual myosin molecules bind to sites on individual actin molecules and draw the thin filaments toward the center of each sarcomere.
• Each myosin head also functions as an ATPase to provide the energy required to power cross-bridge motion. In relaxed muscle, each cross-bridge contains ADP, P_i, and stored energy obtained from the hydrolysis of ATP. The cross-bridge is oriented in the cocked position, loosely attached to actin, and is primed for its next power stroke.
• The regulatory proteins troponin (TN) and tropomyosin (TM), located on the thin filament, inhibit myosin cross-bridges from interacting tightly with actin, except when cytoplasmic Ca²⁺ is elevated. When Ca²⁺ binds to TN-C, it triggers conformational changes that allow myosin cross-bridges to bind tightly to myosin-binding sites on actin molecules and produce a power stroke

Excitation–Contraction Coupling

• The sarcoplasmic reticulum (SR) sequesters Ca²⁺ ions to keep the cytoplasmic concentration of Ca²⁺ low. The terminal cisternae of the SR possess RyR calcium channels. Transverse tubules include voltage-sensitive DHPRs that come into intimate contact with the RyRs of the SR.
• Each skeletal muscle contraction is initiated by an action potential in a motor neuron that releases acetylcholine, which in turn gives rise to a muscle fiber action potential.
• The action potential propagates over the cell membrane of the muscle fiber and depolarizes the DHPRs in the t-tubules. The DHPRs cause the RyR calcium channels to open and allow Ca²⁺ ions to diffuse out of the terminal cisternae of the SR into the cytoplasm.
• Ca²⁺ ions bind to TN and cause conformational changes of TN and TM that expose the myosin-binding sites of adjacent actin molecules. Previously primed myosin heads bind to the actin sites. Repeated cross-bridge cycles continue as long as sufficient Ca²⁺ is present. The cross-bridges move the thick and thin filaments relative to each other, pulling the thin filaments toward the center of the sarcomere.
• Once the muscle fiber action potential is over, the RyR channels close. The Ca²⁺-ATPase pumps of the SR sequester Ca²⁺ back into the SR. As the Ca²⁺ concentration in the cytoplasm decreases, Ca²⁺ dissociates from TN, and the TN–TM complex again prevents actin–myosin interactions. The muscle relaxes. Parvalbumin (prevalent in fast muscles) also binds cytoplasmic Ca²⁺ and thereby enhances the rate of relaxation.

Whole Skeletal Muscles

• Cross-bridge activity within individual muscle fibers accounts for the force generated by a muscle. Force exerted by a muscle is proportional to the cross-sectional area of its contractile elements.
• The tension (force per cross-sectional area) generated by a whole muscle is directly related to the number of actively contracting muscle fibers.
• The amount of tension developed by each contracting fiber in a muscle is determined by the frequency of action potentials from its motor neuron (to produce summation of twitches and tetanus) and the length of the muscle fiber at the time it is stimulated (the length–tension relationship).
• The speed with which a muscle shortens decreases as the load it lifts increases (the load–velocity relationship).
• Work performed by a muscle is the product of force produced by the muscle and the distance it shortens.

Muscle Energetics

• Contractile activity requires the hydrolysis of ATP to provide energy for cross-bridge power strokes and to support the Ca²⁺-ATPase pumps of the sarcoplasmic reticulum.
• ATP is produced by three principal means: (1) transfer of the high-energy phosphate from creatine phosphate to ADP, (2) glycolysis, and (3) oxidative phosphorylation.
• Vertebrate muscle fibers are classified into different types on the basis of their biochemical and metabolic features, and each type is adapted to serve different functions. Muscles usually contain a mixture of different fiber types.
• Muscles adapted for extremely rapid contractions typically produce less tension than muscles that contract at slower rates. The presence of large numbers of mitochondria and abundant SR reduces the cross-sectional area of contractile machinery, and therefore the ability to generate tension.

Neural Control of Skeletal Muscle

• The neuromuscular organization of vertebrates is characterized by many nonoverlapping motor units, each controlled by a single motor neuron. Each muscle fiber within a motor unit generates an action potential that spreads rapidly over the entire cell membrane and triggers contraction.
• Vertebrate tonic fibers are organized into nonoverlapping motor units. They usually do not generate action potentials. Each fiber is innervated by a branch of a motor neuron that makes multiple synaptic contacts along its length. Excitatory postsynaptic potentials (EPSPs) produce local contractions near each synaptic contact.
• The neuromuscular organization of arthropods is characterized by few motor neurons, overlapping motor units, and in some cases, by peripheral inhibition. Each muscle fiber is typically innervated by more than one motor neuron, and each neuron makes multiple synaptic contacts on the fiber. Arthropod muscle fibers typically do not generate action potentials. Instead, the postsynaptic potentials produced at several points along the length of the fiber provide graded electrical signals that each trigger the contractile machinery in a small section of the fiber and control the degree of tension developed. Insect muscles are innervated not only by excitatory and inhibitory neurons but also by neurons that release octopamine or tyramine at synaptic contacts. These transmitters modulate neuromuscular activity and regulate energy metabolism.

Vertebrate Smooth (Unstriated) Muscle

• Smooth muscles make up the walls of tubular and hollow organs, and are found in the eye and at the base of hairs and feathers. Smooth muscles contract slowly because their myosin ATPase isomers hydrolyze ATP very slowly. Some types of smooth muscles maintain contractions for protracted lengths of time using very little energy.
• Smooth muscle cells are small, spindle-shaped, and uninucleate. They contain thin actin filaments and thick myosin filaments arranged around the periphery of the cell. Although the thick and thin filaments overlap with each other, they do not form sarcomeres, which accounts for the muscles’ “smooth” appearance.
• Smooth muscles receive innervation from the autonomic nervous system, and may be influenced by hormones, paracrines, and even stretch. Smooth muscles vary in the number of gap junctions present and in their contractile and electrophysiological properties. Cells in single-unit smooth muscles are connected by numerous gap junctions so that excitation spreads from cell to cell. Cells in multiunit smooth muscles have few gap junctions and function independently of each other. Tonic smooth muscles contract for long periods of time and typically generate only graded membrane depolarizations. Phasic smooth muscles produce rhythmic or intermittent contractions and generate action potentials.
• Smooth muscle contraction is controlled by Ca²⁺, which enters the cytoplasm from the extracellular space or SR and binds to calmodulin. The Ca²⁺–calmodulin complex activates MLCK, which phosphorylates myosin light chains and thereby increases the ATPase activity of the myosin head. Because the number of active cross-bridges in a smooth muscle varies depending on the amount of Ca²⁺ present at any given time, smooth muscle cells are capable of producing graded contractions. Relaxation occurs when cytoplasmic Ca²⁺ decreases, Ca²⁺ unbinds from calmodulin, and MLCK is no longer activated. MLCP dephosphorylates the light chains. Other signaling pathways can influence MLCK and MLCP activity and thus modulate the Ca²⁺ sensitivity of smooth muscle cells.

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