Learning Outcomes - Week 8 - Muscle Flashcards
Know the major functions of muscle and appreciate that there are three different types of muscle
A. The movement of the body (or parts thereof) through the environment. Examples of this function include the virtuosity of Brisbane classical guitarist Karen Schaupp or the power of surfer Molly Picklum .
B. The movements of materials through (or out of) the body. Movements of this type include the movement of blood through the cardiovascular system, the movement of digested food through the gastrointestinal tract, or the slightly less elegant expulsion of gastric contents during vomiting.
C. The maintenance of body temperature through heat production.
There are in fact three different types of muscle tissue in the human body.
The largest proportion (constituting around 40% of total body weight) is the muscle which, for the most part, attaches to the skeleton and is known as skeletal muscle.
The remaining muscle mass (making up 10% of body weight) consists of the muscle found in the heart (cardiac muscle) and smooth muscle which is found primarily in the walls of hollow structures such as blood vessels, the digestive tract and organs of the reproductive systems.
Describe the macro- and microscopic structure of skeletal muscle
Examination of a cross section through most skeletal muscles will reveal that it is spilt up into a number of compartments (known as fascicles) by connective tissue sheaths. Each of these fascicles is in turn made up of a large number of muscle cells which are the basic cellular units of a skeletal muscle. A single muscle cell is known as a muscle fibre. Each muscle fibre is formed during development by the fusion of a number of undifferentiated, mononucleated cells (known as myoblasts) into a single cylindrical, multinucleated cell. Adult skeletal muscle fibres are 10 to 100 micrometres in diameter, and can extend up to 20 cm in length.
As in other cells, the cell or plasma membrane of the muscle fibre (known as the sarcolemma) encloses the cytoplasm (known as sarcoplasm) which contains particularly high concentrations of glycogen (a polymer of glucose) and myoglobin (an oxygen-binding protein). The sarcoplasm contains a large number of mitochondria as well as some other highly specialised cytoplasmic organelles:
Define the subdivision of the nervous system that motoneurones form a part of and be able to describe their structural features.
The contraction of skeletal muscle is under the control of the somatic nervous system which is part of the efferent (motor) division of the nervous system.
The nerve cells whose axons innervate skeletal muscle fibres are known as motoneurones. Their cell bodies are located either in the brainstem or in the anterior horns of the spinal cord. The axons of motoneurons are coated in a fatty material known as a myelin sheath, which is formed by specialised cells called Schwann cells. Motoneurons are the largest-diameter axons in the body. This allows them to conduct electrical signals (action potentials) at high velocities from the central nervous system to skeletal muscle fibres with minimum delay.
Appreciate the functional significance of the fact that motoneurones have myelinated axons.
The myelin sheath is formed during the early years of life, which partly explains why children need time to develop coordinated movement patterns. Individuals affected by certain neurological disorders, such as multiple sclerosis, experience degeneration of the myelin sheath and subsequent loss of coordination.
Describe the structure of the neuromuscular junction and know the functional significance of the major elements.
The myelin sheath ends near the surface of the muscle fibre, and the axon divides into a number of short ‘finger-like’ processes that lie embedded in grooves on the surface of the muscle fibre. The point of contact between axon terminals and the sarcolemma is referred to as the motor end plate. The junction between axon terminals and the motor endplate is known as the neuromuscular junction. In most cases each muscle fibre only receives a contact from one motoneurone. However, each motoneurone (as a consequence of its branching axon) can form a junction with more than one muscle fibre.
Define the term motor unit and understand the impact of motor unit size on the control of movement.
single motoneurone innervates many muscle fibres, but each muscle fibre is controlled by an axon terminal from only one motorneurone. One motoneurone together with all the muscle fibres it innervates is referred to as a motor unit.
Motor unit size varies quite significantly from muscle to muscle with the size being typically small in muscles involved in fine or precise movements and very large in muscles producing large forces requiring less precision.
Explain the mechanism by which an action potential in a motoneurone initiates the contraction of skeletal muscle fibres.
The process by which an action potential in a motoneurone initiates the contraction of all the muscle fibres that it innervates is referred to as neuromuscular transmission and involves a number of distinct stages:
- The action potential arrives at the end of the axon of the motoneurone and triggers the opening of the voltage-gated Ca2+ channels in the axon terminal.
- Ca2+ flows down its concentration gradient from the extracellular fluid into the axon terminal. Ca2+ then binds to proteins that enable synaptic vesicles to fuse with the neuronal plasma membrane, which subsequently results in the exocytosis of acetylcholine into the synaptic cleft which separates the axon terminal and the motor end plate.
- Acetylcholine then diffuses across the cleft and binds to the nicotinic acetylcholine receptors in the folds on the sarcolemma.
- The binding of acetylcholine to these receptors causes a depolarising graded potential in the muscle fibre which is known as the end-plate potential. The reason for this is that the binding of acetylcholine to this receptor triggers the opening of a relatively non-selective cation channel. This allows Na+ to flow into the cell and K+ out of the cell along their respective concentration gradients. However, the differences in electrochemical gradients that exists at the time of channel opening results in more Na+ flowing into the cell than K+ leaving the cell and so the overall effect is a net positive charge entering the cell and hence depolarisation.
- In most instances the magnitude of the endplate potential is 3-4 times greater than that required to reach the action potential threshold for the muscle fibre. Consequently in almost every instance, an action potential in the motoneurone produces an action potential in the muscle fibres it innervates
Understand what is meant by an end-plate potential and how this results in action potential propagation along the length of muscle fibres.
The effect of acetylcholine at the neuromuscular junction is limited by two mechanisms. The first mechanism is simply the diffusion of acetylcholine away from the endplate. The second mechanism involves the degradation of acetylcholine by the acetylcholinesterases found in the cleft.
Note that in most respects the mechanism of neuromuscular transmission is very similar to that of an excitatory postsynaptic potential. However, the magnitude of the end plate potential is much greater than that of an excitatory postsynaptic potential because acetylcholine is released over a larger surface area, and binds to many more receptors, thereby opening many more ion channels. Therefore, one end plate potential is generally more than sufficient to depolarise the sarcolemma to its threshold potential, which results in an action potential.
Most neuromuscular junctions are located near the middle of muscle fibres. Newly generated action potentials produce local ion currents that depolarise adjacent regions, producing more actional potentials at the next site, and so on, to cause action potential propagation. Action potentials propogate from neuromuscular junctions across the surface of the muscle fibre in both directions towards the end of the fibre and throughout the T-tubule network. Note that inhibitory postsynaptic potentials do not occur in human skeletal muscle. All neuromuscular junctions are excitatory
Describe the mechanism of excitation-contraction coupling.
The action potential produced at the end-plate (as a result of neuromuscular transmission) travels along the length of the muscle fibre (in both directions) with a conduction velocity of 1 to 5 m/sec. The mechanisms by which this muscle action potential triggers contraction of the muscle fibre is known as excitation-contraction coupling and involves a number of distinct steps:
A. The action potential travelling along the muscle fibre meets the T-tubules and flows down the T-tubules into the middle of the muscle fibre.
B. The presence of the action potential within the T-tubules triggers the opening of voltage-gated Ca2+ channels in the walls of the sarcoplasmic reticulum.
C. The opening of Ca2+ channels in the sarcoplasmic reticulum enables Ca2+ to run down its concentration gradient into the sarcoplasm and causes the sarcoplasmic Ca2+ concentration to increase from its resting level of 10-7M to around 10-4M.
D. The dramatic increase in sarcoplasm Ca2+ concentration triggers the molecular processes which cause the myofibril to shorten.
E. The myofibrils shorten virtually simultaneously which results in the contraction of the whole muscle fibre.
F. When action potentials stop flowing down the T-tubules, a calcium pump in the membrane of the sarcoplasmic reticulum pumps calcium out of the sarcoplasm and back into the sarcoplsmic reticulum.
G. The Ca2+ concentration within the sarcoplasmic reticulum then returns to resting levels, and myofibrils return to their normal length.
H. The muscle fibre relaxes.
Understand the temporal relationship between an action potential, the tension generated and the sarcoplasmic Ca2+ levels in a single muscle fibre and be able describe how you could record these.
The temoral relationship between the events outlined above is illustrated in the diagram opposite. This shows the results of an experiment performed on a single isolated skeletal muscle fibre in which the muscle fibre action potential (blue) is recorded at the same time as the tension is measured (orange) and the sarcoplasmic Ca2+ concentration monitored (purple) using technique known as calcium imaging.
As you can see, there is a significant delay between the end of the action potential and the beginning of the contraction of the muscle fibre (as indicated by the increase in tension).
This delay reflects the time required for the Ca2+ channels to open, the Ca2+ to enter the sarcoplasm, and the molecular events which lead to myofibril shortening to be initiated. All this adds up to a significant delay between the action potential and the peak force being generated.
One initiated, the mechanical activity within the muscle fibre may last 100 ms or more. Similarly, there is a gradual decline in tension after the peak as the Ca2+ is pumped out of the sarcoplasm, and the myofibrils return to their resting length.
Describe the structure of thin myofilaments.
These filaments are in the order or 5-8 nm in diameter, around 1 micron long and are made up of three constituent proteins:
(i) Two chains of a globular protein molecules known as actin which are twisted around each other to form a double helix, much like two strands of pearls twisted together. Each actin molecule has a high affinity binding site for another protein known as myosin (see below). Actin forms the backbone of thin filaments.
actin
(ii) Two chains of the tube-shaped protein called tropomyosin which are wrapped around the actin helix and positioned in such a way that the myosin binding sites on each molecule of actin are blocked.
(iii) The troponin complex which hold the tropomyosin threads over the myosin binding sites on the actin molecules. Troponin has the ability to do this as a consequence of its three polypeptide units. One polypeptide binds to tropomyosin, another to actin and third which binds Ca2+ and plays a critical role in triggering contraction.
Collectively the actin double helix, the tropomyosin and the troponin complex interact to form a thin filament.
Describe the structure of thick myofilaments.
These thicker filaments are 12-18 nm in diameter and typically 1.6 microns in length. actinEach thick filament is made up of a large number of molecules of the protein myosin all packed together. Myosin makes up about two-thirds of all skeletal muscle protein. Each myosin filament typically is formed by about 200 myosin molecules. One end of each molecule of myosin is made up of two protein strands folded into a globular head, which looks a little like a golf club. If you can imagine the two shafts of the club wrapped around each other with the heads of the clubs sticking out of one end you will sort of get the picture.
The heads (referred to as cross-bridges) each have a binding site for actin (complementary to the myosin binding site on the actin molecules) and an ATPase. A few hundred of these myosin molecules lie parallel to each other with their shafts forming the filament itself and the radiating heads forming the cross-bridges.
Explain how thick and thin myofilamants are arranged and why this results in the typically striated appearance of skeletal muscle.
So the two basic building blocks of the myofibril are these thick and thin filaments, but how do these relatively short proteins interact to form the myofibrils which may run the length of the muscle fibre? The answer to this underlies one of the most striking features of skeletal muscle fibres under the microscope and that is that they have a distinctive striped or ‘striated’ appearance.
The striations observed in the whole muscle fibre represent alternating dark and light bands along the length of myofibrils. Because all the myofibrils in a muscle fibre are similarly aligned, when you look at a skeletal muscle fibre it appears striated. The dark bands are known as A bands, the light bands as I bands and the thin line which is sometimes observed down the middle of the I bands is known as the Z line.
The diagram opposite shows part of a myofibril illustrating the alternating dark and light bands and the nomenclature used to identify the different bands. Also shown is the arrangement of the thick (pink) and thin (blue) filaments that gives rise to the striations.
The alternating dark and light bands are caused by the highly ordered arrangement of the thin and thick filaments within the myofibril. The thick filaments are surrounded by six thin filaments in a hexagonal arrangement.
The dark A-bands represent the regions that contain both the very much denser thick filaments and the less dense thin filaments. The light I-bands represent the regions that contain thin filaments only.
Explain what a sarcomere is and how the sarcomere length changes during muscle contraction and relaxation.
The Z line represents the junctions between successive blocks of thin filaments, and indicates the boundaries of the basic functional unit of a myofibril which is known as a sarcomere. Essentially, whatever happens between the two Z lines is simply repeated again and again along the length of the entire myofibril. Consequently, by observing the changes that take place between two Z lines, we can see what is happening to the entire myofibril.
Describe the molecular interactions between thick and thin filaments that occur during the five distinct stages of the sliding-filament mechanism of muscle contraction.
When a muscle fiber contracts, the overlapping thick and thin filaments in each sarcomere ‘slide’ past each other, propelled by movements of the myosin cross-bridges.
During this shortening of the sarcomeres, there is actually no change in the lengths of either the thick or thin filaments.
Rather, as a result of the filaments sliding past each other, the entire sarcomere shortens in length. Typically duringmuscle movement, one end of the muscle remains at a fixed position, while the other shortens toward the fixed position.
As for excitation-contraction coupling, we will consider the sliding-filament mechanism in a number of distinct stages. Use the key below to identify all the elements in the subsequent figures.
A. Rest:
Prior to any action potential arriving in the muscle fibre the sarcoplasmic Ca2+ concentration is very low. Tropomyosin molecules cover the myosin-binding sites on the actin molecules, thereby preventing the myosin cross-bridges from binding to actin.
The cross-bridges are, however, in an energised or ‘primed’ state as a result of the splitting of ATP molecules. The products of this reaction (ADP and inorganic phosphate) remain bound to the myosin cross-bridges.
This energy storage in myosin is analogous to the storage of potential chemical energy in a stretched spring (i.e., energy has been expended in stretching the spring and remains stored in the spring).
B. Binding:
As a result of the release of calcium from the sarcoplasmic reticulum, the sarcoplasmic Ca2+concentration increases to 10-4M and some of this Ca2+ binds to the calcium binding sites on the troponin complex.
This binding changes the shape of the troponin complex, which in turn displaces the tropomyosin molecules from the myosin-binding sites on the actin molecules.
This process then allows the myosin cross-bridges to bind to the thin filaments. The thick and thin filaments are now coupled.
C. Power Stroke:
The myosin cross-bridge swings over, and binds weakly to a new actin molecule, and is now at an ange of 90 degree relative to the thin filaments. Inorganic phosphate released in this process initiates the ‘power stroke’, whereby the myosin cross-bridge rotates on its hinge, pushing the actin filament past it.
The net effect of this step is that the sarcomere length (the distance between two Z-lines) has decreased because the same process is repeated on both ends of the thick filament.
At the end of this stage the ADP (which is still bound to the ATPase) is released.
D. Detachment:
During the cross-bridge movement, myosin is bound very firmly to actin. This linkage must be broken to allow the cross-bridge to be primed again and repeat the cycle.
The release of the ADP from the ATPase allows a new ATP molecule to bind to myosin, which in turn breaks the link between actin and myosin, allowing them to separate.
If there is still Ca2+ in the sarcoplasm then the tropomyosin filament will still be displaced, the cross bridges are able to bind again to the thin filaments, and the whole cycle is repeated again.
E. Relaxation:
However if there is no Ca2+ available for binding, the troponin complex will return to its original shape and the tropomyosin filaments will resume their blocking position over the myosin binding sites on the thin filaments.
As a consequence, the thick and thin filaments are prevented from binding and will simply slide past each other resulting in the sarcomere length increasing. Note that this means that whereas the contraction of the myofibril requires energy, the relaxation of the myofibril is passive (i.e., does not require energy).
The animation on the right shows ONE complete cross-bridge cycle which begins with the influx of Ca2+ and finishes with the cross-bridge being “primed” again by the break down of ATP. In reality, each cycle only decreases the sarcomere length by approximately 20 nm (around 1% of its total length), whereas a single action potential causes a sarcomere to shorten by around 40%. Obviously this means that the cross-bridge cycle is repeated many times following just a single action potential.