Action Potential and the Role of Myelin

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Action Potential and the Role of Myelin

• Mitul B. Kadakia

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Introduction

• How action potential is generated and its phases
• How action potential propogates
• Role of myelin in action potential propogation
• How myelin is formed, impact of myelin on nerve
  cells

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The Action Potential
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Rising/Overshoot Phase

• Stimulus causes voltage gated Na channels to
  open
• Much higher Na outside cell then inside, thus
  Na rushes inside cell.
• Membrane potential depolarizes and approaches
  ENa
• Membrane potential actually becomes positive
  with respect to external medium, resulting in
  overshoot.

Rising Phase
Overshoot Phase
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Sodium Channel
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Inactivation/Undershoot Phase

• Membrane permeability to Na is shortlived
• K permeability increases temporarily (even more
  than in resting state.)
• More K inside cell than outside (due to Na/K
  pump)
• Membrane thus hyperpolarizes.

Inactivation
Overshoot Phase
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AP originates at axon hillock

• At axon hillock, nerve cells sums up all signals
  coming from dendrites.
• If sum of depolarizing (excitatory) signals minus
  sum of hyperpolarizing (inhibitory signals)
  outweighs the threshold potential, a membrane
  depolarization occurs at the axon potential.

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Action Potential Propogation
Action Potential spreads down axon via Passive
Current Flow
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Passive Current Flow

• Current generated from an action potential flows
  passively down the axon . Occurs by shuttling of
  charge (analogous to wires conducting electricity
  by passing charge).
• This current depolarizes the next region, causing
  a new action potential. As long as enough
  current to break the threshold reaches the next
  region, an AP occurs (all-or-none response)

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Problems with Passive Current Flow alone

• Given current can only travel short distance
  before dissipating. Current leaks out. Large
  voltage drop between nodes.
• Metabolically expensive

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Capacitance

• ?V I/C
• Ability of an nonconductor (i.e. membrane) to
  permits storage of charge

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Action Potential Propogation
R(axon)
R(membrane, C(membrane)
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Improving AP conduction

• Increase axon diameter, thus decreasing R(axon).
• Metabolically Expensive
• Nerves would take up too much space

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Improving AP Conduction

• MYELIN!
• Decreases C(membrane) by increasing distance
  between charges.
• Increase R(membrane) by decreasing nerve cell
  diameter

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Myelin

• 70 lipid, 30 protein, with high concentration
  of cholesterol and phospholipid. Similar to cell
  membrane a good insulator
• Formed by Schwann cells in PNS and
  oligodendrocytes in CNS

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How is Myelin formed?
In CNS, one oligodendrocyte gives rise to myelin
for several nodes. Depends on presence of
astrocytes
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How is Myelin formed?
In development of PNS, Schwann cells line up
along intervals that will eventually become Nodes
of Ranvier. Membrane of Schwann cell surrounds
a axon and forms double membrane structure
mesaxon. Mesaxon elongates and spirals around
axon in concentric layers. At end, cytoplasm
squeezed out and compact myelin sheath formed
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Schwann Cells

• Each node about 1-1.5mm long.
• Thus, as many as 500 Schwann cells on a given axon

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Other functions of Schwann cells

• Clean up PNS debris
• Guide regrowth of damaged PNS axons

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Conduction with myelin

• Current from action potential at a node flows
  through myelinated region.
• Even though its now insulated, some current still
  lost. Thus unmyelinated node required every 1-2
  mm for new action potential to be generated
• AP moves from one node to the next (saltatory
  conduction)
• AP can move quickly across internodes, saves
  metabolic energy

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Why demyelination may lead to nerve death

• In CNS, oligodendrocytes invovled in making
  myelin. Oligodendrocytes also important in
  trophic support for nerve cells. Recent research
  suggests that in MS, oligodendrocytes, not
  myelin, is what is attacked first by immune
  system.
• OLooney, et al. Annals of Neurology 2004

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Why demyelination may lead to nerve death

• In PNS demyelinating diseases (GBS, CIDP), there
  are actually two modes of attack
• Primary demyelination Myelin itself is
  damaged or destroyed
• Secondary demyelination Violent
  inflammation phase which destroys axon itself.
  Nerve signal thus blocked, and thus myelin is
  degenrated.
• Close relationship between Schwann cell and
  neuron (Important for axon regeneration and
  cleanup when axon dies, myelin degenerates)

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Summary

• AP is based on time and voltage dependent
  exchange of Na and K ions
• Myelin plays an important role in action
  potential conduction by increasing speed,
  reducing metabolic demands, and indirectly
  decreasing space needed by nerves.

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Limitations

• Relation between demyelination and cell death is
  unclear what was presented were just hypotheses.

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Sources

• Purves, et al. Neuroscience
• Kandel, et al. Principles of Neuroscience
• OLooney, et al. Annals of Neurology 2004.
• http//www.driesen.com/myelination_-_cns__pns.htm
  
• http//www.jsmarcussen.com/gbs/uk/damage.htm
• Dr. Cardozos lecture, September 2, 2004