Myelin Flashcards
What determines an axons speed
a) Capacitance and resistance of axonal membrane
Internal resistance of axonal cytosol (greater internal resistance = slower conduction velocity)
What is the length factor of an AP
- The distance an AP may travel before it diminishes to an ineffective level
- Determined by charge leakage
What is saltatory conduction in nerve fibres and how does it work?
- To prevent need for wide nerve fibre, mammals adapted saltatory conduction: a process by which nerve impulses propagate along myelinated axons in a jumping fashion between NoR
- Works due to the presence of insulatory myelin sheaths that allow fast conduction velocities while maintaining thin axons
What does myelin do and why is it good? brief
- Myelin increases impulse propagation speed through sequestration of Na and K channels to the nodes of Ranvier
- This reduces energy costs associated with regeneration of membrane potential
How is myelin produced?
- Produced from myelinating glia cells;
Oligodendrocytes in the CNS (can myelinate 10-20 cells); Schwann cells in the PNS (1:1 ratio with neurons)
What differs between Oligodendrocytes and Schwann cells
Oligodendrocytes
- Produced from the ventricular zone of the neuroepithelium
- Serves multiple axons
- Relies on the PLP protein
Schwann cells
- Originate from the neural crest in the sc
- Serve one axon
- Relies on P-zero protein
What is the process ‘Radial sorting’ and its coutcome?
- During development, Schwann cells move along the length of axonal bundles in the sc
- As they do this they proliferate and begin separating axons
- Outcome separates axons into myelinating axons and Remak bundles - ‘cuffs’ of less myelinated, smaller calibre axons that bundle many cells together
How does the physical process of myelination occur?
- Once a larger calibre axon has been sorted, the myelinating axon wraps it up
- The inner MESAXON cuff will start to migrate AROUND the axon repeatedly to form a multi-layer structure (mediated by P-zero)
- Inner mesaxonal cuff is driven by POLYMERISATION OF THE AXON cytoskeleton
- Polymerisation results in infltion while depolymerisation results in deflation and therefore squeezing the cytoplasm forcing movement of the cell
- Unknown stopping mechanism
What does myelin actually do?
- Increases impulse propagation speed through sequestration of Na and K channels to the nodes of Ranvier (Saltatory conduction)
- Reduction of energy cost associated with regeneration of membrane potential
- Compact wiring
What are features of the following areas:
a) Nodal membrane
b) Paranodal junctions
c) Juxtaparanodal domain
d) Internode
a) the region of exposed axon membrane with a high concentration of Na+ and K+ channels
b) These are specialised regions adjacent to the NoR where the myelin sheath attaches to the axonal membrane. These consist of cell-adhesion complexes
c) Immediately adjacent to the paranodal junctions, extending away from the NoR. Contain a high concentration of K+ channels that are crucial in the refractory period of the AP
d) area covered by the myelin sheath
Contactin and Caspr are proteins at which junction? And with what glial protein do they form complexes?
Paranodal junctions and NF155
In Schwann cells in the PNS only, there are microvilli that are related to proteins that are instrumental in the direction of Na+ channels to the NoR
What proteins are involved in this process (3)
Cilia are enriched in GLIOMEDIN (just on glia) and NrCAM (on both glia and axon) form complexes with the axonal protein NF186
These molecules associate with Na+ channels directly
Building on the above card, briefly describe the mechanism of node formation in myelinated cells
- Hemi nodal clustering of Na+ channels is the result of the paranodal complexes involving gliomedin, NrCAM and NF186
Peripheral neurons are not protected by a bony structure like CNS neurons are so they are endowed with other protective attributes.
What is the:
a) Epineurium
b) Perineurium
c) Endoneurium
and what are their attributes
a) Covers a number of fascicles made up of groups of peripheral nerves
b) Is the coating around one fascicle
c) Coating within the fascicle consisting of lots of collagen
What is Guillain-Barre Syndrome?
- This is a peripheral condition in which the immune system attacks the peripheral nerves
- Acquired after food poisoning because of antigenic mimicry of the bacterial surface proteins with neuronal surface proteins
Describe Charcot-Marie-Tooth Disease? (what gene / protein causes it)
- Major cause of CMT is a duplication of chromosome 17 resulting in a triple dose of gene PMP22 that codes a myelin integrin protein (61% of CMT cases)
- This duplication causes destabilisation of the myelin sheath
- Reduced efficiency sequestering Na+ and K+ channels
- Key feature = muscle wastage - result of death of unmyelinated axons
There are multiple types of CMT. What are they and what causes them? (tough)
CMT1A: Duplication of gene on chromosome 17, results in onion bulb formation
CMT1B: Mutation in gene for p-zero
CMT2: Abnormalities in peripheral nerve axon
CMT3: Severe demyelinating, point mutation in P-zero or PMP22 genes
CMT4: Recessive demyelinating motor and sensory neuropathies
CMTX: Mutation in connexin-32 gene on X chromosome
What are the roles of PMP22 and P-zero
PMP22:
- Important for the integrity of myelin sheaths
- Codes a myelin integrin protein
- Mutations cause CMTs (CMT1A and CMT3)
P-Zero
- Present in peripheral nerves, crucial protein in myelin structure
- Mutations also cause CMTs (CMT1B and CMT3)
What does demyelination mean for the cell?
- Shorter internodes and thinner myelin sheaths result in reduced conduction velocities
- Also may result in redistribution of Na+ and K+ channels leading to conduction blocks
What is immune-mediated polyneuropathy?
- Polyneuropathy refers to neuropathy of sensory AND motor fibres
- Patient has developed antibodies against proteins in the nodal structure (such as Caspr-connectin complexes)
What is the potential role of myelination in circuit fine tuning?
- Myelination is flexible
- Partial myelination may contribute to learning processes by fine tuning timings of specific circuits
- Similar concept to delay lines
