Skeletal Muscle and the Neuromuscular Junction Flashcards
State the characteristics of muscle.
- contractility
- excitability
- extensibility
- elasticity
Skeletal muscles do not normally contract in the absence of nervous stimulation. TRUE or FALSE?
TRUE
Muscle fibres are made up of myofibrils are composed of __________ and ___________ filaments.
actin and myosin
There are syncytial bridges between cells in skeletal muscles. TRUE or FALSE?
FALSE.
There are no syncytial bridges between cells in skeletal muscles.
NOTE:
~ Syncytium: a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei
~ There are no syncytial bridges between cells. Instead, the muscle fibers are made up of myofibrils, which are divisible into individual filaments. These myofilaments contain several proteins that together make up the contractile machinery of the skeletal muscle.
The contractile mechanism in skeletal muscle largely depends on the proteins myosin-II, actin, tropomyosin, and troponin. Troponin is made up of three subunits:
troponin I, troponin T, and troponin C.
a) The form of myosin found in muscle is ______________, with two globular heads and a long tail.
b) The heads of the myosin molecules form _____________________ with actin.
a) myosin-II
b) cross-bridges
a) Myosin contains heavy chains and light chains, and its heads are made up of the: light chains and the
_____________________ of the heavy chains
b) The myosin heads contain two sites. Name them.
a) amino terminal portions
b) actin-binding site and catalytic site that hydrolyzes ATP.
The thin filaments are polymers made up of two chains of actin that form a long double helix. ____________________ molecules are long filaments located in the groove between the two chains in the actin.
Tropomyosin
Describe the role of the components of the troponin complex in muscle contraction.
Troponins are additional proteins attached intermittently along the sides of the tropomyosin molecules. These protein molecules are actually complexes of three loosely bound protein subunits, each of which plays a specific role in controlling muscle contraction.
Troponin C binds calcium and activates thin filaments.
Troponin I binds actin and inhibits contraction in the absence of calcium.
Troponin T binds tropomyosin and attaches troponin to the thin filament.
[Diagram]
Outline the steps involved in neuromuscular transmission.
(a) An action potential is propagated down the motoneuron until the presynaptic terminal is depolarized.
(b) Depolarization of the presynaptic terminal causes voltage-gated Ca2+ channels to open, and calcium flows into the nerve terminal.
(c) Uptake of Ca2+ into the nerve terminal causes exocytosis of stored acetylcholine (ACh) into the synaptic cleft.
(d) ACh diffuses across the synaptic cleft to the muscle end plate, where it binds to nicotinic ACh receptors (AChRs).
(e) The nicotinic AChR is also an ion channel for Na+ and K+. When ACh binds to the receptor, the channel opens.
(f) Opening of the channel causes both Na+ and K+ to flow down their respective electrochemical gradients. As a result, depolarization occurs. [Note: although potassium exits the muscle cell when ACh receptors are open, sodium entry and depolarization dominate.]
(g) This depolarization is called the end plate potential, and if strong enough, will result in depolarization of adjacent muscle membrane to its firing level.
(h) Acetylcholine is then removed from the synaptic cleft by acetylcholinesterase, which is present in high concentration at the NMJ.
What is the pathophysiologic basis of myasthenia gravis?
In the autoimmune disease, myasthenia gravis, antibodies are made against the acetylcholine receptors of the neuromuscular junction in skeletal muscle. These antibodies bind to the acetylcholine receptor on the postsynaptic membrane and block acetylcholine binding.
Therefore, while normal action potentials occur in the motoneurons and ACh is released normally, the ACh cannot cause depolarization of muscle end plates. Without depolarization of muscle end plates, there can be no action potentials or contraction in the muscle.
Describe the steps in excitation-contraction coupling that permit the cross-bridge cycle of muscle contraction.
(a) An action potential is initiated and propagated in motor neuron axon arriving at the presynaptic terminal and causing voltage-gated Ca++ channels to open.
(b) Calcium ions enter the pre-synaptic terminal and initiate the release of ACh from synaptic vesicles.
(c) ACh is released into the synaptic cleft by exocytosis.
(d) ACh diffuses across the synaptic cleft and binds to nicotinic acetylcholine receptors on the motor end plate, opening Na+, K+ ion channels.
(e) More Na+ moves into the fiber at the motor end plate than K+ moves out, depolarizing the membrane, producing the end-plate potential (EPP).
(f) ACh is rapidly degraded in the synaptic cleft to acetic acid and choline by acetylcholinesterase, thus limiting the length of time acetylcholine is bound to its receptor site. The result is that one presynaptic action potential produces one postsynaptic action potential in each muscle fiber.
(g) The action potential produced in a muscle fiber is propagated from the postsynaptic membrane near the middle of the fiber toward both ends and into the T tubules.
(h) Depolarization of the sarcolemma triggers dihydropyridine receptors [voltage-gated, L-type calcium channels] to open, allowing Ca++ influx. In skeletal muscle, DHPRs are mechanically coupled to ryanodine receptors, which are calcium channels found on the sarcoplasmic reticulum, thus more Ca++ is released into the cytoplasm. This is known as calcium-induced calcium release.
(i) Ca++ binds to troponin C on the thin filaments, uncovering myosin-binding sites on actin, causing tropomyosin to move away from its blocking position.
Explain the steps in the cross-bridge cycle that leads to muscle contraction.
Myosin heads bind to actin when ATP is hydrolysed to ADP and inorganic phosphate (Pi).
This binding forms a cross-bridge, and the myosin head moves, pulling the actin filament toward the center of the sarcomere (power stroke).
ADP is released, resulting in a stronger attachment of myosin to actin (rigor state).
In the absence of ATP, myosin remains bound to actin, causing muscle rigidity (as seen in rigor mortis).
ATP binding causes myosin to detach from actin.
ATP hydrolysis re-cocks the myosin head, preparing it for the next cycle of attachment and pulling.
Multiple myosin heads on thick filaments cycle asynchronously to maintain constant tension in activated muscle fibers.
