Chapter 9: Muscle

3 ways muscle can form atp

(1) phosphorylation of ADP by creatine phosphate (a small molecule produced from three amino acids and capable of functioning as a phosphate donor), (2) oxidative phosphorylation of ADP in the mitochondria, and (3) phosphorylation of ADP by the glycolytic pathway in the cytosol.

satellite cells

If skeletal muscle fibers are damaged or destroyed after birth as a result of injury, they undergo a repair process involving a population of undifferentiated stem cells known as satellite cells. Satellite cells are normally quiescent, located between the plasma membrane and surrounding basement membrane along the length of muscle fibers. In response to strain or injury, they become active and undergo mitotic proliferation. Daughter cells then differentiate into myoblasts that can either fuse together to form new fibers or fuse with stressed or damaged muscle fibers to reinforce and repair them. The capacity for forming new skeletal muscle fibers is considerable but may not restore a severely damaged muscle to the original number of muscle fibers. Some of the compensation for a loss of muscle tissue also occurs through a satellite cell-mediated hypertrophy (increase in size) of the remaining muscle fibers. Muscle hypertrophy also occurs in response to heavy exercise. Evidence suggests that this occurs through a combination of hypertrophy of existing fibers, splitting of existing fibers, and satellite cell proliferation, differentiation, and fusion. Many hormones and growth factors are involved in regulating these processes, such as growth hormone, insulin-like growth factor, and sex hormones.

3 types of muscle fibers

Slow-oxidative fibers (type I) combine low myosin-ATPase activity with high oxidative capacity. Fast-oxidative-glycolytic fibers (type IIa) combine high myosin-ATPase activity with high oxidative capacity and intermediate glycolytic capacity. Fast-glycolytic fibers (type IIb) combine high myosin-ATPase activity with high glycolytic capacity.

resting muscle fiber cross bridge

The cross-bridges in a resting muscle fiber are in an energized state resulting from the splitting of ATP, and the hydrolysis products ADP and inorganic phosphate (Pi) are still bound to myosin (in the chemical representation, bound elements are separated by a dot, while detached elements are separated by a plus sign). This energy storage in myosin is analogous to the storage of potential energy in a stretched spring.

cross bridge cycle steps

The sequence of events that occurs between the time a cross-bridge binds to a thin filament, moves, and then is set to repeat the process is known as a cross-bridge cycle. Each cycle consists of four steps: (1) attachment of the cross-bridge to a thin filament; (2) movement of the cross-bridge, producing tension in the thin filament; (3) detachment of the cross-bridge from the thin filament; and (4) energizing the cross-bridge so it can again attach to a thin filament and repeat the cycle. Each cross-bridge undergoes its own cycle of movement independently of other cross-bridges. At any instant during contraction, only some of the cross-bridges are attached to the thin filaments, producing tension, while others are simultaneously in a detached portion of their cycle.

muscle tendon

The term muscle refers to a number of skeletal muscle fibers bound together by connective tissue (Figure 9.2). Skeletal muscles are usually attached to bones by bundles of connective tissue consisting of collagen fibers known as tendons.

thick filament structure

The thick filaments are composed almost entirely of the protein myosin. The myosin molecule is composed of two large polypeptide heavy chains and four smaller light chains. These polypeptides combine to form a molecule that consists of two globular heads (containing heavy and light chains) and a long tail formed by the two intertwined heavy chains. The tail of each myosin molecule lies along the axis of the thick filament, and the two globular heads extend out to the sides, forming cross-bridges, which make contact with the thin filament and exert force during muscle contraction. Each globular head contains two binding sites, one for attaching to the thin filament and one for ATP. The ATP binding site also functions as an enzyme (called myosin-ATPase) that hydrolyzes the bound ATP, harnessing its energy for contraction.

disruption of neuromuscular signaling

There are many ways by which disease or drugs can modify events at the neuromuscular junction. For example, curare, a deadly arrowhead poison still used by some indigenous peoples of South America, binds strongly to nicotinic ACh receptors. It does not open their ion channels, however, and is resistant to destruction by acetylcholinesterase. When a receptor is occupied by curare, ACh cannot bind to the receptor. Therefore, although the motor neurons still conduct normal action potentials and release ACh, there is no resulting EPP in the motor end plate and no contraction. Because the skeletal muscles responsible for breathing, like all skeletal muscles, depend upon neuromuscular transmission to initiate their contraction, curare poisoning can cause death by asphyxiation. Neuromuscular transmission can also be blocked by inhibiting acetylcholinesterase. Some organophosphates, which are the main ingredients in certain pesticides and "nerve gases" (the latter originally developed as insecticides and later for chemical warfare), inhibit this enzyme. In the presence of these chemicals, ACh is released normally upon the arrival of an action potential at the axon terminal and binds to the end-plate receptors. The ACh is not destroyed, however, because the acetylcholinesterase is inhibited. The ion channels in the end plate therefore remain open, producing a maintained depolarization of the end plate and the muscle plasma membrane adjacent to the end plate. A skeletal muscle membrane maintained in a depolarized state cannot generate action potentials because the voltage-gated Na+ channels in the membrane become inactivated, which requires repolarization to reverse, just as happens in neurons. After prolonged exposure to ACh, the receptors of the motor end plate become insensitive to it, preventing any further depolarization. Thus, the muscle does not contract in response to subsequent nerve stimulation, and the result is skeletal muscle paralysis and death from asphyxiation. Nerve gases also cause ACh to build up at muscarinic synapses (see Chapter 6, Section C), for example, where parasympathetic neurons inhibit cardiac pacemaker cells. This can result in an extreme slowing of the heart rate, virtually halting blood flow through the body. The antidote for organophosphate and nerve gas exposure includes both pralidoxime, a drug that reactivates acetylcholinesterase, and atropine, a muscarinic receptor antagonist described in Chapter 6. Drugs that block neuromuscular transmission are sometimes used in small amounts to prevent muscular contractions during certain types of surgical procedures, when it is necessary to immobilize the surgical field. One example is succinylcholine, which actually acts as an agonist to the ACh receptors and produces a depolarizing/desensitizing block similar to acetylcholinesterase inhibitors. Nondepolarizing neuromuscular junction blocking drugs that act more like curare and last longer are also used, such as rocuronium and vecuronium. The use of such paralytic agents in surgery reduces the required dose of general anesthetic, allowing patients to recover faster and with fewer complications. Patients must be artificially ventilated, however, to maintain respiration until the drugs have cleared from their bodies. Page 263 Another group of substances, including the toxin produced by the bacterium Clostridium botulinum, blocks the release of acetylcholine from axon terminals. Botulinum toxin is an enzyme that breaks down proteins of the SNARE complex that are required for the binding and fusion of ACh vesicles with the plasma membrane of the axon terminal (review Figure 6.27). This toxin, which produces the food poisoning called botulism, is one of the most potent poisons known. Application of botulinum toxin to block ACh release at neuromuscular junctions and other sites is increasingly being used for clinical and cosmetic procedures, including the inhibition of overactive extraocular muscles, prevention of excessive sweat gland activity, treatment of migraine headaches, and reduction of aging-related skin wrinkles. Having described how action potentials in motor neurons initiate action potentials in skeletal muscle cells, we will now examine how that excitation results in muscle contraction.

concentric contraction eccentric contraction

both isotonic contractions concentric: tension greater than load, shortening eccentric: load greater than tension, lengthening

latent period

few milliseconds following an action potential before the tension in the muscle fiber begins to increase during this latent period, processes associated with excitation-contraction coupling are occuring

tension

force exerted on an object by a contracting muscle

load

force exerted on the muscle by an object (usually its weight) muscle tension and load are opposing forces to move load, muscle tension must be greater than the opposing load

twitch

mechanical response of a muscle fiber to a single action potential

isotonic contraction

muscle changes length while the load on the muscle remains constant isotonic=constant tension

isometric contraction

muscle develops tension but does not shorten or lengthen when muscle supports a load in a constant position or attempts to move an otherwise supported load that is greater than the tension developed by the muscle

thin filament structure

thin filaments (which are about half the diameter of the thick filaments) are principally composed of the protein actin, as well as two other proteins—troponin and tropomyosin—that have important functions in regulating contraction. An actin molecule is a globular protein composed of a single polypeptide (a monomer) that polymerizes with other actin monomers to form a polymer made up of two intertwined, helical chains. These chains make up the core of a thin filament. Each actin molecule contains a binding site for myosin.

contraction time

time interval from beginning of tension development at the end of the latent period to peak tension