Muscle structure and pathologies Flashcards
Describe the histological appearance of skeletal muscle
- cylindrical cells
- striated
- multinucleate
- cm in length
- limited regeneration (satellite cells)
- voluntary control
Describe the histological appearance of cardiac muscle
- Branched cells with intercalated disks
- striated
- mono/binucleate
- length: 100 μm
- no regeneration
- spontaneous contraction
Describe the histological appearance of smooth muscle
- Spindle shaped
- central nucleus
- length: 20-200μm
- regenerate
- found in vessels, hollow organs, glands
- regulated by ANS and endocrine system
Describe the organisation of skeletal muscle
A muscle is surrounded by epimysium (tough dense connective tissue sheath)
Groups of muscle fascicles form a muscle. Muscle fascicles are surrounded by perimysium. Blood vessels, lymphatics and nerves are contained in the perimysium
Muscle fascicles contain groups of muscle fibres
Muscle fibres are individual muscle cells which have fused their membranes together and created one multinucleated cell. Therefore, muscle fibres are sometimes referred to as “muscle cells”. The cell membrane of a muscle fibre is the sarcolemma. Muscle fibres are surrounded by endomysium (thin loose connective tissue). Capillaries and nerve fibres are found in the endomysium.
Myofibrils make up muscle fibres . Myofibrils are formed from arrangements of myofilaments (actin and myosin) which are the contractile element.
Describe Type 1 muscle fibres
(slow twitch)
- Aerobic respiration
- Slow oxidative respiration
- Lots of mitochondria
- Slow contraction, fatigue resistant
Describe Type 2A muscle fibres
- Aerobic and anaerobic respiration
- Fast oxidative respiration
- Lots of mitochondria
- Intermediate contraction
Describe Type 2B muscle fibres
(Fast twitch)
- Anaerobic respiration
- Few mitochondria
- Fast powerful contraction, rapidly fatiguable
Define motor unit
Motor unit = the motor neurone and the muscle fibres it innervates.
Describe the stages of transmission at the NMJ
1) Action potential arrives and depolarises the pre-synaptic membrane of the motor neurone.
2) This triggers opening of voltage-gated calcium channels. Calcium moves into the pre-synaptic terminal down its electrochemical gradient.
3) Vesicles containing acetylcholine (ACh) move to the pre-synaptic membrane, fuse with the membrane, and release the ACh into the synaptic cleft by exocytosis.
4) ACh diffuses across the synaptic cleft and binds to nicotinic ACh receptors on the post-synaptic membrane (also called the motor end plate) (don’t get nicotinic ACh receptors mixed up with muscarinic Ach receptors which are G-protein coupled receptors on smooth muscle).
5) Nicotinic receptors are ligand-gated ion channels. Binding of Ach induces a conformational change in the receptor which opens the channel, allowing Na+ to enter to the motor end plate, and K+ to leave. The motor end plate depolarises creating an end plate potential
6) The end plate potentiate is usually sufficient to stimulate opening of voltage-gated sodium channels in the adjacent membrane which initiates an action potential which propagates down the muscle fibre.
7) ACh only binds briefly to the nicotinic receptors and dissociates. It is broken down in the synaptic cleft by the enzyme acetylcholinesterase (AChE) into acetate and choline, which is taken up into the pre-synaptic terminal and recycled.
Describe the changes in myasthenia gravis
- Autoantibodies against nicotinic acetylcholine receptors on the post-synaptic membrane
- Commonly affects extraocular muscles, facial muscles, and bulbar muscles
- Muscle weakness and fatigability of voluntary muscles. Can reverse with ice test.
What is the treatment for myasthenia gravis?
acetylcholinesterase inhibitors (e.g. neostigmine)
Describe the effects of botulinum toxin
- Produced by Clostridium botulinum
- Degrades the SNARE protein complex
- Block acetylcholine release from pre-synaptic terminals -> total blockade at the NMJ
- Results in paralysis (flaccid – LMN)
- Botulinum toxin A (botox) has medical uses, dystonias, ocular conditions
What is a sarcomere?
The basic contractile unit / the functional unit of contraction.
The region between two Z-lines.
What is the A band?
located in the centre of the sarcomere. Mainly thick filament, but some overlapping thin filaments. Appears dark under a light microscope.
What is the I band?
x 2, located either side of the A band . Contain thin filaments only (not overlapping) and appear light under a light microscope
What are the Z discs/lines?
darkly staining lines which run down the middle of each I band. Indicate the point where thin actin fibres from adjacent sarcomeres join. The region between two Z lines is called a sarcomere.
What is the H zone?
area in the centre of the A band where there only thick filaments (no overlapping filaments)
What is the M line?
point at which the thick filaments meet and connect with the cell membrane
What do the heads of the myosin molecule contain?
An actin binding site and an ATPase site
What three proteins are the thin filaments composed of?
actin, tropomyosin and troponin.
Define excitation-contraction coupling
the mechanism that translates a muscle action potential into muscle contraction
What are the steps involved in excitation-contraction coupling?
1) Depolarisation of muscle fibre membrane (sarcolemma)
2) Action potential is propagated to the T tubules, carrying a wave of depolarisation to the interior of the muscle fibre
3) Depolarisation of T tubules causes a conformational change in their voltage-gated dihydropyridine receptors
4) These receptors are in mechanical contact with ryanodine receptors of the sarcoplasmic reticulum. Conformational change in the dihydropyridine receptors causes a conformational change in the ryanodine receptors which open to release calcium from storage in the sarcoplasmic reticulum into the intracellular fluid of the muscle fibre, increasing the intracellular calcium concentration
5) Calcium binds to troponin C on thin filaments, inducing a conformational change in the troponin complex which moves the tropomyosin molecule, exposing the myosin-binding site of the actin molecule
6) Cross-bridges are formed between the actin molecule and myosin heads
What is the sliding filament theory?
The mechanism of contraction is caused by the thick and thin filaments sliding over each other.
What are the steps of cross-bridge cycling?
1) Binding of calcium to troponin C displaces tropomyosin and allows myosin heads to bind to actin forming cross-bridges. Initially the myosin head is bound tightly to actin in the rigor position. ATP is required to reduce the affinity of myosin for actin and allow to move, and if ATP is absent then this binding is permanent resulting in rigor mortis.
2) ATP binds to the myosin head and induces a conformational change, reducing the affinity of the myosin head for actin. The myosin head releases actin.
3) ATP is hydrolysed to ADP and inorganic Phosphate (Pi) by ATPase which initially both remain bound to the myosin head. The release of energy from the hydrolysis of ATP changes the conformational state of the myosin head further. The myosin head is cocked/bent into a high energy position. It is like a spring which has been loaded. The myosin head binds to actin at a point further along from its original binding site.
4) Phosphate is released from the myosin head and the myosin head springs back into it’s original position and pushes the actin molecule towards the M-line. The thick and thin filaments slide over each other, shortening the sarcomere. This is called the power stroke.
5) ADP is released and the myosin head binds tightly to the actin again (rigor position). As long as ATP is available and calcium remains bound to troponin C, the cross-bridge cycling will continue and the myosin will walk along the actin filament. Remember that there are multiple myosin heads bound to an actin filament during this cycle.
