Unit 3
What are the components of the neuromuscular junction (NMJ)? What neurotransmitter is released from a motor neuron? What event leads to the release of this neurotransmitter? How does this neurotransmitter stimulate a muscle action potential? Describe the entire NMJ activity. How are acetylcholine levels regulated to terminate a contraction (and cause relaxation)?
euromuscular junction (NMJ) , the synapse between a somatic motor neuron and a skeletal muscle fiber synapse: is a region where communication occurs between two neurons, or between a neuron and a target cell—in this case, between a somatic motor neuron and a muscle fiber. At most synapses a small gap, synaptic cleft: separates the two cells. neurotransmitter: Because the cells do not physically touch, the action potential cannot "jump the gap" from one cell to another. Instead, the first cell communicates with the second by releasing a chemical called a neurotransmitter axon terminal:At the NMJ, the end of the motor neuron, divides into a cluster of synaptic end bulbs: the neural part of the NMJ. synaptic vesicles.:Suspended in the cytosol within each synaptic end bulb are hundreds of membrane-enclosed sacs called synaptic vesicles. acetylcholine:Inside each synaptic vesicle are thousands of molecules of abbreviated ACh,the neurotransmitter released at the NMJ. motor end plate: The region of the sarcolemma opposite the synaptic end bulbs, is the muscle fiber part of the NMJ. Within each motor end plate are 30 million to 40 million acetylcholine receptors: integral transmembrane proteins to which ACh specifically binds. These receptors are abundant in junctional folds: deep grooves in the motor end plate that provide a large surface area for ACh. A nerve impulse (nerve action potential) elicits a muscle action potential in the following way ●1 Release of acetylcholine. Arrival of the nerve impulse at the synaptic end bulbs stimulates voltage-gated channels to open. Because calcium ions are more concentrated in the extracellular fluid, Ca2 flows inward through the open channels. The entering Ca2 in turn stimulates the synaptic vesicles to undergo exocytosis. During exocytosis, the synaptic vesicles fuse with the motor neuron's plasma membrane, liberating ACh into the synaptic cleft. The ACh then diffuses across the synaptic cleft between the motor neuron and the motor end plate. ●2 Activation of ACh receptors. Binding of two molecules of ACh to the receptor on the motor end plate opens an ion channel in the ACh receptor. Once the channel is open, small cations, most importantly Na, can flow across the membrane. ●3 Production of muscle action potential. The inflow of Na (down its electrochemical gradient) makes the inside of the muscle fiber more positively charged. This change in the membrane potential triggers a muscle action potential. Each nerve impulse normally elicits one muscle action potential. The muscle action potential then propagates along the sarcolemma into the system of T tubules. This causes the sarcoplasmic reticulum to release its stored Ca2 into the sarcoplasm and the muscle fiber subsequently contracts. ●4 Termination of ACh activity. The effect of ACh binding lasts only briefly because ACh is rapidly broken down by an enzyme called acetylcholinesterase, or AChE . This enzyme is attached to collagen fibers in the extracellular matrix of the synaptic cleft. AChE breaks down ACh into acetyl and choline, products that cannot activate the ACh receptor
In detail, describe excitation-contraction coupling. How is it related to the contraction cycle? How are calcium levels regulated to terminate contraction (and cause relaxation)?
An increase in Ca2 concentration in the sarcoplasm starts muscle contraction, and a decrease stops it. When a muscle fiber is relaxed, the concentration of Ca2 in its sarcoplasm is very low,only about 0.1 micromole per liter (0.1 mol/L). However, a huge amount of Ca2 is stored inside the sarcoplasmic reticulum As a muscle action potential propagates along the sarcolemma and into the T tubules, it causes Ca2 release channels in the SR membrane to open When these channels open, Ca2 flows out of the SR into the sarcoplasm around the thick and thin filaments. As a result, the Ca2 concentration in the sarcoplasm rises tenfold or more. The released calcium ions combine with troponin, causing it to change shape.This conformational change moves tropomyosin away from the myosin-binding sites on actin. Once these binding sites are free, myosin heads bind to them to form cross-bridges, and the contraction cycle begins. The events just described are referred to collectively as excitation-contraction coupling, as they are the steps that connect excitation (a muscle action potential propagating along the sarcolemma and into the T tubules) to contraction (sliding of the filaments).
In detail, describe the contraction cycle and explain the four steps of the cycle. Describe how rigor mortis occurs.
At the onset of contraction, the sarcoplasmic reticulum releases calcium ions (Ca2) into the sarcoplasm. There, they bind to troponin. Troponin then moves tropomyosin away from the myosin-binding sites on actin. Once the binding sites are "free," the contraction cycle—the repeating sequence of events that causes the filaments to slide—begins. The contraction cycle consists of four steps: 1. ATP hydrolysis. The myosin head includes an ATP-binding site and an ATPase, an enzyme that hydrolyzes ATP into ADP (adenosine diphosphate) and a phosphate group. This hydrolysis reaction reorients and energizes the myosin head. Notice that the products of ATP hydrolysis—ADP and a phosphate group—are still attached to the myosin head. 2. Attachment of myosin to actin to form cross-bridges. The energized myosin head attaches to the myosin-binding site onactin and releases the previously hydrolyzed phosphate group. When the myosin heads attach to actin during contraction, they are referred to as cross-bridges. 3. Power stroke. After the cross-bridges form, the power stroke occurs. During the power stroke, the site on the cross-bridge where ADP is still bound opens. As a result,the cross-bridge rotates and releases the ADP. The crossbridge generates force as it rotates toward the center of the sarcomere, sliding the thin filament past the thick filament toward the M line. 4. Detachment of myosin from actin. At the end of the power stroke, the cross-bridge remains firmly attached to actin until it binds another molecule of ATP. As ATP binds to the ATP binding site on the myosin head, the myosin head detaches from actin. Rigor mortis: After death, cellular membranes become leaky. Calcium ions leak out of the sarcoplasmic reticulum into the sarcoplasm and allow myosin heads to bind to actin. ATP synthesis ceases shortly after breathing stops, however, so the cross-bridges cannot detach from actin. The resulting condition, in which muscles are in a state of rigidity (cannot contract or stretch), is called rigor mortis (rigidity of death). Rigor mortis begins 3-4 hours after death and lasts about 24 hours; then it disappears as proteolytic enzymes from lysosomes digest the cross-bridges.
What is the role of ATP in muscle contraction? How is ATP produced by muscle cells? Describe the roles of creatine phosphate, anaerobic respiration and aerobic respiration. For how long can each of these sources produce ATP?
Huge amount of ATP is needed to power the contraction cycle. to pump ca2+ into the SR and for other metabolic reactions. muscle fibers have ATP present to only power for a few seconds. If more time the muscle fibers must make ATP in three ways: 1. Creatine Phosphate: energy-rich molecule that is found in muscle fiber. Creatine Phosphate is synthesis from excess ATP. Creatine kinase catalyzes the transfer of a high-energy phosphate group from creatine phosphate to ADP to form new ATP molecules. Together Creatine Phosphate and ATP provide enough energy for the muscle to contract about 15 sec 2. Anaerobic(glycolysis) cellular respiration: does not require oxygen glucose is catabolized to generate ATP glucose easily pass from the blood to contracting muscle fibers via unfacilliated diffusion glycolysis breaks down each glucose molecule into 2 mol of pyruvic acid. it occurs in the cytosol and produces a net gain of 2 molecules of ATP most of the pyruvic acid is converted to lactic acid in the cytosol and diffuses out of the skeletal muscle fibers into the blood. 3. aerobic cellular respiration: pyruvic acid enters the mitochondria where it is completely oxidized that generates ATP, water co2, and heat
Describe the microanatomy of a myofibril
Thin filaments: are 8 nm in diameter and 1-2 m long† and composed mostly of the protein actin, Thick filaments: are 16 nm in diameter and 1-2 m long and composed mostly of the protein myosin. Both thin and thick filaments are directly involved in the contractile process Z discs: Narrow, plate-shaped regions of dense material that separate one sarcomere from the next. A band: Dark, middle part of sarcomere that extends entire length of thick filaments and includes those parts of thin filaments that overlap thick filaments. I band: Lighter, less dense area of sarcomere that contains remainder of thin filaments but no thick filaments. A Z disc passes through center of each I band. H zone: Narrow region in center of each A band that contains thick filaments but no thin filaments. M line: Region in center of H zone that contains proteins that hold thick filaments together at center of sarcomere.
How do botox and curare affect the NMJ?
curare: a poison used by South American Indians on arrows and blowgun darts, causes muscle paralysis by binding to and blocking ACh receptors. In the presence of curare, the ion channels do not open. Curare-like drugs are often used during surgery to relax skeletal muscles Botox: Botulinum toxin produced by the bacterium Clostridium botulinum, blocks exocytosis of synaptic vesicles at the NMJ. As a result, ACh is not released, and muscle contraction does not occur. The bacteria proliferate in improperly canned foods, and their toxin is one of the most lethal chemicals known. A tiny amount can cause death by paralyzing skeletal muscles. Breathing stops due to paralysis of respiratory muscles, including the diaphragm. Injections of Botox into the affected muscles can help patients who have strabismus (crossed eyes), blepharospasm (uncontrollable blinking), or spasms of the vocal cords that interfere with speech. It is also used to alleviate chronic back pain due to muscle spasms in the lumbar region and as a cosmetic treatment to relax muscles that cause facial wrinkles
What is a muscle twitch? Diagram the following on a Force/Tension graph: muscle twitch, wave summation, and tetany. What is responsible for the latent period?
twitch contraction is the brief contraction of all muscle fibers in a motor unit in response to a single action potential in it motor neuron. A twitch is recorded when a stimulus that results in contraction (force) of a single muscle fiber is measured over a very brief millisecond time frame. Two motor units, one in green, the other in purple, demonstrate the concept of progressive activation of a muscle known as recruitment Recruitment allows a muscle to accomplish increasing gradations of contractile strength There is a brief delay called the latent period as the AP sweeps over the sarcolemma and Ca2+ ions are released from the sarcoplasmic reticulum (SR) During the next phase the fiber is actively contracting This is followed by relaxation as the Ca2+ ions are re- sequestered into the SR and myosin binding sites are covered by tropomyosin Temporary loss of excitability is call the refractory period - All muscle fibers in a motor unit will not respond to a stimulus during this short time
