Muscles Flashcards
What is the structure of terminal ends of motor neurones?
- At the end of a motor neurone, the axon becomes unmyelinated and separates into multiple branches (1-2 μm).
- At the end of each branch, there is a plate-like structure called a bouton which forms the pre-synaptic terminal between the motor neurone and one muscle fibre.
What is the name given to all muscle fibres innervated by one motor neurone?
Motor unit
What is the structure of a neuromuscular junction (NMJ)?
- On the post-synaptic membrane (sarclemma), there’s inward invaginations every 1-2 μm called junctional folds.
- Above each junctional fold is a thickening in the bouton called the active zone.
- Within each active zone are rows of thousands of neurotransmitter vesicles.
- These vesicles fuse with the pre-synaptic membrane within these zones and are released into synaptic cleft by exocytosis.
What is the basal lamina?
- In the synaptic cleft is a network of proteins (e.g. collagen, laminin) and mucopolysaccharides.
- This forms the glue that ‘sticks’ the end plate to the sarcolemma.
- This also contains high concentration of AChE to terminate synaptic transmission.
What is the width of the synaptic cleft?
~50 nm
What is the sequence of events that occur at NMJ during synaptic transmission?
- AP arrives at bouton (post-synaptic terminal) and depolarises it.
- Depolarisation causes voltage-gated Ca2+ channels to open, which causes an influx of Ca2+ down electrochemical gradient and an increase in intracellular [Ca2+].
- Increase in intracellular [Ca2+] increases the probability of ACh vesicles fusing with the pre-synaptic membrane in the active zones.
- Vesicles fuse with pre-synaptic membrane and ACh is released into the synaptic cleft by exocytosis.
- ACh diffuses across the synaptic cleft and binds to AChR, opening associated ion channels and causing influx of Na+ which depolarises the sarcolemma (EPP).
- Depolarisation causes opening of voltage-gated Na+ channels (in the folds), which causes AP to occur.
- ACh is broken down by AChE in the synaptic cleft into acetate and chlorine that diffuse back into the bouton where they are re-synthesised into ACh.
What is the enzyme that synthesises ACh?
Choline acetyltransferase (from choline and Acetyl-CoA)
What is the synaptic delay and what is responsible for it?
- Delay between the time of action potential arrival at the pre-synaptic terminal and the time an EPP occurs in post-synaptic terminal.
- The time taken for Ca2+ to cause vesicle fusion is thought to be mainly responsible for this delay.
What is the relationship between [Ca2+] and probability of vesicle fusion?
Probability is proportional to [Ca2+]^4
What is the structure of the AChR?
- N1 ACh receptor
- Ligand-gated ion channel
- 5 subunits (2α, β, γ, δ)
- ACh binding sites located on the α subunits?
What are the advantages of having 2 ACh binding sites?
- Opening probability proportional to [ACh]^2
- Prevents channel from opening when ACh is very low but dramatically increases opening probability of channels when [ACh] is high.
What are the kinematics of the AChR?
- 2 ACh molecules need to bind to both sites on the AChR before it opens.
- Over-stimulation causes AChR to inactivate, preventing depletion of trans-membrane ionic gradients.
What is the resting potential of muscles?
~-90 mV
What is the reversal potential of AChRs?
~0 mV
What is the function of curare in research?
Blocks AChRs and allows EPSPs to be observed.
What is the function of physostigmine in research?
Allows the amount of ACh released on stimulation of pre-synaptic terminal to be measured.
what is the pathophysiology of myasthemia gravis?
- Autoimmune disease.
- Caused by autoimmune attacks on AChRs, reducing their numbers and preventing stimulation of skeletal muscles.
- Causes weakness and paralysis of skeletal muscles.
What was concluded from the observation of MEPPs?
ACh was stored and released from the pre-synaptic terminal in packets (quanta). This suggested that ACh was stored in vesicles.
What are the characteristics of ACh release during EPPs?
- When multiple EPPs were measured in low extenal [Ca2+], a pattern was observed.
- About each multiple of 0.4 mV was a normally distributed curve called a ‘bin’. Each bin represented a fixed number of ACh molecules released and the normal distribution of the bins represented the variations in ACh content of each vesicle.
- The peaks of each bin formed a poisson distribution. This showed that the probability of each vesicle fusing with the presynaptic membrane is independent of each other, but is increased with an increase in intracellular [Ca2+].
What are the proteins involved in release of ACh by exocytosis?
Vesicle:
- Synaptobrevin (v-SNARE): Binds to t-SNAREs on the pre-synaptic membrane.
- Synaptotagmin: Ca2+ sensor.
Pre-synaptic membrane:
- Syntaxin (v-SNARE): Binds to snaptobrevin.
- SNAP-25 (v-SNARE): Binds to synaptobrevin.
- n-SEC-1: Inhibits syntaxin.
Recycling:
- α-SNAP
- NSF (ATPase)
What is the general structure of muscles?
Muscle → Fascicles → Muscle fibres → Myofibrils → Sarcomeres
What are the features of a skeletal muscle fibre?
- Sarcolemma: Plasma membrane
- Sarcoplasm: Cytoplasm
- Transverse (T-) tubules: Involved in EC coupling
- Sarcoplasmic reticulum: Specialised endoplasmic reticulum acting as Ca2+ store
- Nuclei: Muscle fibres are multinucleate
- Mitochondria: Produces ATP for cross-bridge cycling
- Myofibrils: Contractile mechanism
What is the diameter of a muscle fibre?
50-100 μm
What is the significance of titin in skeletal muscles?
- Titin is a protein believed to attach myosin to the Z-disc.
- It has a role in generation passive tension in muscles.
- It also has vital role in determining the length-tension relationship of muscle via the lattice rearrangement model.