BCS 205 Unit 3 Skeletal Muscles

myosin

Each thick filament is composed of many molecules of the contractile protein myosin. That myosin looks somewhat like two golf clubs twisted together, with two globular "heads" and two intertwining polypeptide chains making up a "tail." The heads protrude from the myosin tail on a "neck." The neck of each myosin molecule is flexible where it meets the tail at a point called the hinge. Each myosin head includes a site that binds to a thin filament, among other functional components we'll discuss later. The myosin molecules are arranged within the thick filament in such a way that clusters of myosin heads are found at each end, with only myosin tails found in the middle.

sarcoplasmic reticulum (muscle endoplasmic reticulum that stores calcium)

-The SR is a modified smooth endoplasmic reticulum that forms a weblike network surrounding each myofibri -Surrounding the myofibrils like a web is the sarcoplasmic reticulum, or SR, which is a modified smooth endoplasmic reticulum. Its primary function is the storage and release of calcium ions, activities vital to muscle contraction and relaxation.

What is cross bridge cycling?

A myosin head bound to an actin molecule is known as a crossbridge. When this binding occurs, a crossbridge cycle is initiated that leads to the sliding of myofilaments. A muscle contraction is simply a succession of crossbridge cycles and the resulting production of force. During these cycles, the myosin head grabs onto a series of actin molecules in the thin filament, pulling the filament progressively closer to the M line of the sarcomere.

troponin

A second regulatory protein is the smaller, globular troponin that holds the tropomyosin in place.

actin

A thin filament consists of many molecules of the contractile protein actin. This bead-shaped protein has an area, called the active site, that can bind to a myosin head. Multiple actin subunits string together like beads on a necklace to form the largest part of the thin filament. This actin "string" appears as two intertwining strands in the functional thin filament.

neuromuscular junction

All skeletal muscle fibers are innervated, which means they are connected to a neuron. A single neuron called a motor neuron communicates with many muscle fibers; each connection is referred to as a synapse (SIN-aps; syn- = "clasp together"). The synapse of a motor neuron with a muscle fiber is known as the neuromuscular junction, or NMJ. The function of the neuromuscular junction is to transmit a signal, called a nerve impulse (which is actually an action potential of the neuron), from the neuron to the sarcolemma of the muscle fiber. In this example of the Cell-Cell Communication Core Principle , neurons communicate with muscle fibers at the neuromuscular junction. Each NMJ consists of three parts: the axon terminal, synaptic cleft, and motor end plate

axon terminal

Axon terminal. The motor neuron extends a long "arm" or cytoplasmic extension, called an axon, to the muscle fiber. The end of the axon swells to form an axon terminal, or synaptic bulb, which contains synaptic vesicles. These vesicles have neurotransmitters, chemicals that, when released, trigger changes in the target cells of the neuron. The neurotransmitter in the axon terminals of motor neurons that connect to skeletal muscle fibers is acetylcholine .

What additional cation (besides sodium and potassium) plays a large role in muscle contraction?

Calcium

myasthenia gravis

a chronic autoimmune disease that affects the neuromuscular junction and produces serious weakness of voluntary muscles

What neurotransmitter is responsible for skeletal muscle contraction?

acetylcholine skeletal muscle fibers must be excited in order to contract, but what this means more specifically is that the sarcolemma of a muscle fiber will not have an action potential without stimulation by ACh from a motor neuron. Once the muscle fiber is excited by such stimulation, a process called excitation-contraction coupling conveys this excitation to the parts of the fiber that produce the contraction, the myofilaments. Then one type of myofilament is able to slide past the other. The sarcomere contracts, and contractions in many sarcomeres produce contraction of the whole muscle. So the process of muscle contraction can be broken down into three parts: the excitation phase, excitation-contraction coupling, and the contraction phase.

Where is cation calcium in muscle contraction stored?

binds to troponin

sequence of events of the crossbridge cycle

Preparation for contraction Calcium ions bind to troponin. The regulatory protein troponin has three subunits: One binds calcium ions, one binds actin, and the other tropomyosin. In this step, calcium ions bind to the appropriate troponin subunit. Tropomyosin moves, and the active sites of actin are exposed. The binding of calcium ions causes troponin to shift its position, allowing tropomyosin to move away from the active sites. When the active sites of actin are exposed, the myosin heads are able to bind tightly to them. A myosin head bound to an actin molecule is known as a crossbridge. When this binding occurs, a crossbridge cycle is initiated that leads to the sliding of myofilaments. A muscle contraction is simply a succession of crossbridge cycles and the resulting production of force. During these cycles, the myosin head grabs onto a series of actin molecules in the thin filament, pulling the filament progressively closer to the M line of the sarcomere.

motor end plate

The motor end plate is a specialized region of the sarcolemma, whose folded surface contains many receptors for ACh. Recall that a receptor is a protein within the plasma membrane that binds to a specific ligand. These receptors are actually ligand-gated ion channels; ACh is the ligand.

transverse tubule (infolding of sarcolemma into the muscle cell)

The plasma membrane of the muscle fiber is called by a different name because its structure is different. The sarcolemma isn't confined to the exterior of the cell—it forms inward extensions called transverse tubules (or T-tubules) that dive deeply into the muscle fiber and surround each myofibril. The T-tubules form a tunnel-like network within the muscle fiber. These tunnels are continuous with the exterior of the cell and so are filled with extracellular fluid. Flanking each side of a T-tubule are enlarged portions of the SR called terminal cisternae. The combination of a T-tubule and the two terminal cisternae on either side is known as a triad

sarcolemma (muscle cell membrane)

The sarcolemma is composed of a phospholipid bilayer with multiple specialized integral and peripheral proteins. -descriptor of sarcolemma: plasma membrane is replaced with sarcolemma

Synaptic Cleft

The synaptic cleft is the narrow space between the axon terminal and the muscle fiber into which ACh is released. It is filled with collagen fibers and an extracellular gel that anchors the neuron in place. It also contains enzymes that break down ACh.

Tetanus

• Clostridium tetani spores - anaerobe found in soil; in diseased tissue, transforms into rod-shaped bacterium; produces toxin • Reaches spinal cord and brainstem via retrograde axonal transport; causes increased muscle tone, painful spasms, widespread autonomic instability; diaphragm doesn't work • Predisposing factors: penetrating injury, co-infection with other bacteria, devitalized tissue, foreign body, localized ischemia

Duchenne's muscular dystrophy

• DMD is a degenerative muscular disease occurring in boys • Caused by a defective gene for the protein dystrophin; recessive X-linked genetic transmission • Symptoms arise between 2 and 12 years of age; include weakness of the proximal limb muscles and a waddling gait; generally wheelchair-bound by age 12 and dead from respiratory or cardiac failure by age 20 • Treatment - approved by FDA September 2016; not a cure; only works for a minority of patients (Know that Duchenne's muscular dystrophy is a hereditary degenerative muscle disease in boys)

Creatine Supplementation

• Research shows that supplementation with creatine does improve performance in top athletes by milliseconds for activities that require short bursts of muscle activity such as sprinting • Effects on endurance-type activities are minimal to nonexistent • Creatine may actually be detrimental in some cases: Causes weight gain from water retention Massive doses may cause kidney damage • Skeletal muscles have a maximal storage capacity for creatine; huge doses are a WASTE OF MONEY; excess excreted in urine

Botulism

• The bacterium Clostridium botulinum produces the most lethal known biological poison - as little as one gram of crystalline toxin is enough to kill about one million adults • Exposure to the botulinum toxin through contaminated food causes botulism: The toxin binds to motor neurons of the NMJ and blocks the release of acetylcholine from synaptic vesicles This paralyzes the affected muscle, and without proper treatment, death from respiratory failure will follow • Can be used to treat painful muscle spasm and migraine headaches when injected in minute quantities; also used cosmetically to relax facial muscles (as Botox)

Think back to cellular respiration. Glycolysis can produce a little bit of ATP quickly and anaerobically. Electron chain transport can produce a lot of ATP in the presence of oxygen. Which process applies to high intensity, short duration muscle contraction like sprinting? Which process applies to low intensity, longer duration muscle contraction like walking? This is explained well in the muscle lab introduction towards the end.

-When contraction begins, the main immediate energy source of the muscle fiber is stored as ATP. This ATP is rapidly consumed, but is regenerated almost immediately by a reaction using a molecule called creatine phosphate. Creatine phosphate, found primarily in muscle fibers, is about 5-6 times more abundant than ATP in the cytosol. During the creatine phosphate reaction, creatine phosphate, with the help of the enzyme creatine kinase (KY-nayz; CK), donates a phosphate group to ADP, producing ATP: DP+Creatinephosphate⇄CKATP+Creatine ATP produced by this reaction provides the muscles with enough energy for about an additional 10 seconds of maximal muscle activity. Though this may not sound like much, it's enough for a short burst of activity, such as a 100-meter sprint -When immediate energy sources are depleted, muscle fibers turn to glycolysis, also known as glycolytic or anaerobic catabolism, to make ATP.Regardless of the amount of stored glycogen, though, glycolysis by itself can provide adequate ATP for only about 30-40 seconds of sustained muscle contraction. -Combined, immediate and anaerobic glycolytic energy sources are adequate for short bursts of activity, such as running a 400-meter race. However, longer-lasting muscle activity requires a muscle fiber to use mostly oxidative or aerobic catabolism to generate ATP

sequence of events of the contraction cycle

ATP hydrolysis "cocks" the myosin head. Muscle contraction requires energy provided by the hydrolysis of ATP. Each myosin head contains both a site that binds to ATP and an ATPase enzyme that breaks down ATP. When ATP binds to the head of the myosin molecule, the ATPase in the myosin rapidly hydrolyzes the ATP to ADP and a phosphate group (P). The energy liberated from this reaction "cocks" the myosin head into its high-energy position, ready to work. The ADP and phosphate remain attached to the myosin head when it is cocked. The myosin head binds to actin. With the myosin head in its cocked position, it may now bind to the active site of actin. Note that the resulting crossbridge is at about a 90° angle relative to the thick filament. The power stroke occurs when the ADP and phosphate detach from the myosin head; myosin pulls actin toward the center of the sarcomere. The ADP and phosphate (inorganic phosphate, represented as Pi ) detach from the myosin head as it pivots on its hinge and moves from its cocked high-energy position to its relaxed (or low-energy) position. As the myosin pivots, it pulls the actin toward the center of the sarcomere. This action is known as the power stroke. Notice that the myosin crossbridge is now at about a 45° angle relative to the thick filament. ATP breaks the attachment of myosin to actin. Another ATP binds to the myosin head, which breaks its attachment to actin

the sequence of events of muscle relaxation

Acetylcholinesterase degrades the remaining ACh, and the final repolarization occurs. The AChE breaks down the ACh remaining in the synaptic cleft, degrading it into substances that can no longer stimulate the muscle. Without such stimulation, the ligand-gated ion channels in the motor end plate close, and the sarcolemma goes through the final repolarization of the contraction. The sarcolemma returns to its resting membrane potential, and calcium ion channels in the SR close. The sarcolemma returns to its resting state once repolarization is complete. The calcium ion channels in the SR then close, so no further release of calcium ions from the SR takes place. Calcium ions are pumped back into the SR, returning the calcium ion concentration in the cytosol to its resting level. Active transport pumps in the SR membrane consume ATP to pump calcium ions from the cytosol back into the SR. This activity decreases the calcium ion concentration of the cytosol, returning it to resting level. Troponin and tropomyosin block the active sites of actin, and the muscle relaxes. As the cytosolic concentration of calcium ions returns to its resting level, calcium ions dissociate from troponin. This causes troponin to return to its original position, pushing tropomyosin back to where it blocks the active sites. This blocking prohibits the myosin heads from binding to actin, and the muscle contraction is over. The myofilaments then slide back into their original positions, with support from titin and other structural proteins. The calcium ion pumps and AChE work all the time to allow relaxation of a muscle fiber. This makes it possible for the fiber to start a new contraction when a new stimulus comes along

myofibril (specialized organelle in muscle cell)

Muscle cells also have unique structures that allow them to serve their functions. You can see in Figure 10.2 that the sarcoplasm of muscle cells contains cylindrical organelles called myofibrils . All three types of muscle cells contain myofibrils, although they are arranged differently in smooth muscle cells than in skeletal and cardiac cells. Myofibrils are essentially bundles of specialized proteins, including those involved in muscle contraction. A myofibril measures about 1 μm in diameter, or about 1100 the thickness of a human hair. Each muscle cell has hundreds to thousands of myofibrils—they make up about 50-80% of its volume—and other organelles such as mitochondria are found packed between them.

steps of excitation-contraction coupling

The end-plate potential stimulates an action potential. The end-plate potential opens enough voltage-gated sodium ion channels in areas of the sarcolemma adjacent to the motor end plate, stimulating an action potential. The action potential is propagated down the T-tubules. The action potential propagates like a wave along the sarcolemma, as depolarization of one area of the membrane triggers the next few voltage-gated sodium ion channels to open. This process continues like a chain reaction down the muscle fiber. Ultimately, the wave of depolarization dives deeply into the muscle fiber via the T-tubules. T-tubule depolarization leads to the opening of calcium ion channels in the SR, and calcium ions enter the cytosol. Electrical changes in the T-tubules in turn trigger changes in proteins in the terminal cisternae of the SR, which flank either side of the T-tubule in a triad. The T-tubules are directly linked to the terminal cisternae by voltage-gated proteins. When the T-tubules depolarize, these proteins "twist" open the calcium ion channels in the terminal cisternae. In essence, these proteins open the "floodgates" of the SR, releasing many calcium ions into the cytosol. As calcium ions flood the cytosol, the sarcolemma is repolarizing

sarcomere (functional unit of contraction)

The functional unit of contraction—where muscle tension is produced—is the sarcomere. A sarcomere is the section of a myofibril that extends from one Z-disc to the next Z-disc (Z comes from the German word zwischen, which means "between"). Each sarcomere, then, includes a full A band and half of two I bands.

tropomysin

The long, ropelike regulatory protein called tropomyosin spirals around the two actin strands so that, at rest, it covers the active sites on actin.