Myelin Flashcards
What type of channels are found in the dendritic domain?
Ligand gated
What type of channels are found in the soma/axon?
why?
voltage gated
What are the three properties that determine speed and efficiency of AP?
- capacity of axonal membrane
- resistance of axonal membrane
- internal resistance of membrane in cytosol
What is the difference in how the squid versus vertabrates evolutionary response to the need for speed?
Giant squid have a HUGE diameter in their escape response circuitry (the lower the internal resistance the higher the conduction velocity, big=fast) but this is huge metabolic burden, so vertabrates evolved to have myelin sheaths which speeds up conductance
Which cells produce myelin?
oligodendrocytes- in the CNS
Schwann cells- in the PNS
What are the differences between Schwann cells and oligodendrocytes?
- number of axons (1 schwann per 1 axon; 1 oligodendrocyte per 10-20 axons)
- Embryonic origin (schwann: neural crest; oligodendrocyte: neurepithelium)
- Biochemistry (schwann major protein: p-zero; oligodendrocyte: PLP)
major protein important for structure of myelin sheath
What are the signalling molecules involved in Na channel adhesion at the nodes of Ranvier?
- NrCAM: on glia and node
- Gliomedin: on glia
- NF186: on node, connects Na channel to ankyrin and spectrin in node
What are the signalling molecules involved in cell adhesion at the paranodal junction?
- Contactin: on axon
- Caspr: on axon
- NF155: on glia
Why is gliomedin important? Whats the evidence for it and what does it tell us?
In gliomedin KO mice, there are no Na channels at the heminodes:
- inital clustering of Na channels is gliomedin dependent (and advancing schwann cell membrane)
- must be mechanism that fences in Na channels and links them to axonal membrane at nodes of ranvier
What two mechanisms are responsible for Na clustering at nodes of ranvier?
- Signalling molecules (gliomedin, NrCAM, NF186)
- Fencing in by advancing mylein membrane
What protects neurons in PNS vs CNS?
- Connective tissue in PNS (epineurim, perineurum, endoneurium)
- Bones in CNS
What neurological diseases is mylein implicated in?
Multiple sclerosis
Guillian barre syndrome: immune system attacks sheaths and neurons
Charcot marie tooth disease: hereditary motor and sensory neuropathy
Describe the pathogenesis of charcot-marie-tooth disease in relation to demyleination
genetic mutation results in tripple production of PMP22 (mylein integrin protein) and thus destabilisation of myelin sheaths
Results in
- onion bulb formation and **nerve thickening **
- remyelination: shorter internodes and thinner myelin
- conduction block: redistribution of Na and K channels means weaker currents and can cause insufficient depolarization
when myelin sheath is lost, and reattachment fails, then it reverts to immature phenotype and starts over again (doesnt die)
p-zero mutation is also implicated in CMT
How does myelin affect conduction properties?
The sheaths push Na channels and K channels to the nodes of ranvier- so membrane potential only needs to be regenerated here instead of entire length of axon aka salutory conduction. Thus sheaths
- increase impulse propagations
- reduce energy cost
- allow compact wiring
Myelin 1) increases membrane resistance (less leakage) and 2) decreases membrane capacitance (increases the distance between inner charge n outer charge so less capacity to hold charge bc less attraction)
How is the mylein sheath formed?
After neural crest formation, Schwann cells grow along the length of the axon during devleopment and sort them into large and small calibre axons. The small calibre axons are bundled together into remak bundles. The schwann cell wraps itself around the large calibre axon and compacts (via p-zero/PLP), and the actin cytoskeletal network drives the schwann cell membrane wrapping around the axon (via polymerization and demolymerization)
