Muscles

myofibrils

- thin "tubes" that span the length of the fiber and show the banding pattern - A single muscle fiber contains hundreds to thousands of myofibrils that run parallel to its length.

What are motor units and what is their significance?

A motor unit consists of a motor neuron and all of the muscle fibers that are innervated by that motor neuron. a. Motor neurons emanate from the spinal cord, so severing of the spinal cord interrupts the flow of information. b. Any given motor neuron innervates two muscle fibers some distance from each other (not right next to each other) c. Degree of contraction depends on how many motor units are activated d. When we knowingly want to lift something heavy, more motor neurons are activated

What is the relationship between a muscle, a muscle fiber, a myofibril, a sarcomere, thick filaments, thin filaments?

A muscle is an organ that contains many fasiculi. Fasiculi are wrapped in connective tissue and contain many muscle fibers. Muscle fibers are multinucleate cells that are made up of many myofibrils. Sarcomeres are the structural components that make up myofibrils. Sarcomeres consist of thin filaments and thick filaments.

t-tubule system

At each A band—I band junction, the sarcolemma of the muscle cell protrudes deep into the cell interior, forming an elongated tube called the T tubule. The T tubules tremendously increase the muscle fiber's surface area.

How would a lack of calcium affect muscle function? Where is calcium involved?

Calcium entry triggers the release of ACh into the synaptic cleft, so cross bridge formation requires calcium and calcium ions promote muscle cell contraction.

What part of muscle contraction would be most directly impaired in the absence of abundant ATP?

Cross bridge attachment requires ATP. In the absence of ATP, myosin heads will not detach from actin (the cross bridge will not break), causing rigor mortis.

What is an ideal sarcomere length and what does that really mean in terms of contraction?

The optimal operating length for a muscle fiber is the length at which it can generate maximum force. Within a sarcomere, the ideal length-tension relationship occurs when a muscle is slightly stretched and the thin and thick filaments overlap optimally, because this relationship permits sliding along nearly the entire length of the thin filaments. If a muscle fiber stretches so much that the filaments do not overlap, the myosin heads have nothing to attach to and cannot generate tension. Alternatively, if the sarcomeres are so compressed and cramped that the Z discs abut the thick myofilaments, and the thin filaments touch and interfere with one another, little or no further shortening can occur. Optimal sarcomere length is 80% - 120% of the resting length. At this ideal length, a muscle generates maximum force. Increases and decreases beyond this optimal length reduce its force and ability to generate tension.

What are some of the important characteristics of myosin? How are these organized in the filament? Why is that significant from a functional perspective?

Thick filaments are primarily composed of the protein myosin. Each myosin molecule consists of two heavy and four light polypeptide chains, and has a rodlike tail attached by a flexible hinge to two intertwined helical polypeptide heavy chains. The globular heads, each associated with two light chains, are the "business end" of myosin. During contraction, they link the thin and thick filaments together, forming cross bridges, and swivel around their point of attachment. These cross bridges act as motors to generate muscular contractile force.

What aspect of muscle structure and function would be affected by weight lifting?

When one works out a lot, they have more myofibrils, so muscle fibers increase in size, ultimately increasing muscle mass.

multinucleate cells

a muscle fiber is an elongated multinucleate cell; the multinucleated nature of muscle cells allows for rapid coordination of contraction along the whole length of the fiber

Describe all the specific steps that are involved in the contraction of a muscle starting with a motor neuron releasing acetylcholine at the neuromuscular junction and ending with contraction followed by relaxation again.

a. Action potential arrives at axon terminal of motor neuron. b. Voltage-gated Ca2+ channels open. Ca2+ enters the axon terminal moving down its electrochemical gradient. c. Ca2+ entry causes ACh (a neurotransmitter) to be released by exocytosis. d. ACh diffuses across the synaptic cleft and binds to its receptors in the sarcolemma. e. ACh binding opens ion channels in the receptors that allow simultaneous passage of Na+ into the muscle fiber and K+ out of the muscle fiber. More Na+ ions enter than K+ ions exit, which produces a local change in the membrane potential called the end plate potential. f. ACh effects are terminated by its breakdown in the synaptic cleft by acetylcholinesterase and diffusion away from the junction. g. An end plate potential is generated at the neuromuscular junction. h. Depolarization: Generating and propagating an action potential (AP). i. The local depolarization current spreads to adjacent areas of the sarcolemma. This opens voltage-gated sodium channels there, so Na+ enters following its electrochemical gradient and initiates the AP. The AP is propagated as its local depolarization wave spreads to adjacent areas of the sarcolemma, opening voltage-gated channels there. Again Na+ diffuses into the cell following its electrochemical gradient. i. Repolarization: Restoring the sarcolemma to its initial polarized state (negative inside, positive outside). i. Repolarization occurs as Na+ channels close (inactivate) and voltage-gated K+ channels open. Because K+ concentration is substantially higher inside the cell than in the extracellular fluid, K+ diffuses rapidly out of the muscle fiber. j. The action potential (AP) propagates along the sarcolemma and down the T tubules. k. Calcium ions are released. i. Transmission of the AP along the T tubules of the triad causes the voltage-sensitive tubule proteins to change shape. This shape change opens the Ca2+ release channels in the terminal cisterns of the sarcoplasmic reticulum, allowing Ca2+ to follow into the cytosol. l. Calcium binds to troponin and removes the blocking action of tropomyosin. i. When Ca2+ binds, troponin changes shape, exposing binding sites for myosin (active sites) on the thin filaments. m. Contraction begins: Myosin binding to actin forms cross bridges and contraction (cross bridge cycling) begins. At this point, E-C coupling is over.

What is the difference between isometric and isotonic "contraction"?

a. Concentric isotonic contraction: On stimulation, muscle develops enough tension (force) to lift the load (weight). Once the resistance is overcome, the muscle shortens and the tension remains constant for the rest of the contraction. b. Isometric contraction: Muscle is attached to a weight that exceeds the muscle's peak tension-developing capabilities. When stimulated, the tension increases to the muscle's peak tension-developing capability, but the muscle does not shorten.

What happens to the sarcomere during contraction? How do each of the "bands" look - do they lengthen, shorten, or stay the same? What happens to the filaments?

a. The sarcomere gets shorter b. A bands stay the same c. I bands get shorter d. Z lines get closer to each other e. H zones get shorter (and disappear) f. The thick and thin filaments slide past each other

sarcoplasmic reticulum

an elaborate smooth endoplasmic reticulum; its interconnecting tubules surround each myofibril the way the sleeve of a loosely crocheted sweater surrounds your arm. Most SR run longitudinally along the myofibril, communicating with each other at the H zone. The SR regulates intracellular levels of ionic calcium. It stores calcium and releases it on demand when the muscle fiber is stimulated to contract. Calcium provides the final "go" signal for contraction.

banding pattern

muscle fibers have a banded (striated) appearance. The banding pattern arises from orderly arrangement of smaller structures called myofilaments. As the muscle contracts, the sarcomeres shorten and the appearance of the band pattern changes.

lateral sacs

sarcoplasmic reticulum in muscle cells contain lateral sacs that are close to the T-tubule system; they are filled with calcium

sarcomeres

the structural components of myofibrils composed of thin and thick filaments which are composed of specific proteins

What are the molecular components of thin filaments? What is each of their roles in the contraction process?

- Composed of Actin, Troponin, and Tropomyosin - Two strands of actin subunits are wound around each other - Troponin and Tropomyosin are regulatory in allowing or disallowing muscle contraction to happen. Troponin is a globular three-polypeptide complex. One of its polypeptides, TnI, is an inhibitory subunit that binds to action. Another (TnT) binds to tropomyosin and helps position it on actin. Troponin molecules are also calcium binding. Tropomyosin strands spiral about the actin core and help to stiffen and stabilize it. Successive tropomyosin molecules are arranged end to end along the actin filaments, and in a relaxed muscle fiber, they block myosin-binding sites on actin so that myosin heads on the thick filaments cannot bind to the thin filaments. (Myosin needs to bind to actin for contraction, but when contraction cannot/ does not occur, it is because the active site for myosin is covered or blocked by tropomyosin.)

What are thick filaments and what are they composed of?

- Primarily composed of Myosin (a few hundred molecules per filament) - Two heavy and two sets of 2 light chains - Arranged in a way that looks like a golf club - Oriented in a way that the heads face outward - Have hinges and ATPase activity crucial for function Thick filaments are myosin-containing filaments that extend the entire length of the A band and are connected in the middle of the sarcomere at the M line. Each thick filament contains about 300 myosin molecules bundled together, with their tails forming the central part of the thick filament and their heads facing outward at the end of each thick filament. As a result, the central portion of a thick filament (in the H zone) is smooth, but its ends are studded with a staggered array of myosin heads. The heads bear actin and ATP-binding sites and also have intrinsic ATPase activity that spits ATP to generate energy for muscle contraction.

What are the possible ways a muscle cell can use to produce energy? What are the rough time lines for these - how long can such a supply last?

Direct phosphorylation i. Coupled reaction of creatine phosphate (CP) and ADP 1. CP can donate a phosphate to ADP production of ATP ii. Energy source: CP iii. Oxygen use: none iv. Products: 1 ATP per CP v. Duration of energy provision: 15 seconds Anaerobic pathway i. Glycolysis and lactic acid formation 1. In conversion of pyruvic acid to lactic acid, NAD+ is regenerated 2. Lactic acid is an indication to muscle that not enough oxygen is available ii. Energy source: glucose iii. Oxygen use: none iv. Products: 2 ATP per glucose, lactic acid v. Duration of energy provision: 60 seconds, or slightly more Aerobic pathway i. Aerobic cellular respiration ii. Energy source: glucose, pyruvic acid, free fatty acids from adipose tissue, amino acids from protein catabolism iii. Oxygen use: required iv. Products: 32 ATP per glucose, CO2, H20 v. Duration of energy production: hours

Describe a cycle of contraction and relaxation (in terms of the thick/thin filament interactions).

During contraction, the thin filaments slide past the thick filaments so that the actin and myosin filaments overlap to a greater degree.