The structure and function of
myelinated nerve
Mark Baker
Neuroscience
• Learning Objectives (all knowledge
based):
• Provide an explanation of how impulses
are propagated
• Describe how myelin works
Resting potentials and action
potentials
Inside
Outside
120 mM K+
2 mM K+
K+ channels
10 mM Na+
140 mM Na+
Na+ channel
Outside
Inside
+ve
120 mM K+
d -ve
10 mM Na+
+ve
2 mM K+
K+ channels
140 mM Na+
Na+ channel
Outside
Inside
120 mM K+
2 mM K+
K+ channels
-80 mV
10 mM Na+
140 mM Na+
Na+ channel
Outside
Inside
120 mM K+
2 mM K+
K+ channels
-80 mV
10 mM Na+
140 mM Na+
Na+ channel
• Reversal potential (E) for an ion is given
by the Nernst equation:
• At 20 ºC, 58.2 log [out]/[in]
• At 37 ºC, 61.5 log [out]/[in]
• Thus a normal value of EK is negative and
ENa is positive
Na+ current generates upswing of action potential
Na+ channel inactivation
and K+ channel activation
underlie repolarization
K+ channel activation
generates
afterhyperpolarization
Function of myelinated nerve
Function of myelinated nerve
nerve conducts action potentials by local circuit
currents
potentials
longitudinal currents
recorded
extracellularly
outside
local circuit current
transmembrane
current
direction of impulse
inside
axon
compact myelin
Shiverer mouse
(myelin basic
protein null)
internode
node of Ranvier
optic nerve axons (Brady et al 1999)
Function of myelinated nerve
Tasaki 1959
R
single fibre
teased out
2
0
-2
0
1
2 ms
transmembrane current
at a node
node
internode
current (nA)
current (nA)
air gaps
R
2
0
-2
0
1
2 ms
current
across the myelin
Function of myelinated nerve
Tasaki 1959
R
2
single fibre
teased out
outward current
0
-2
inward current
0
1
2 ms
transmembrane current
at a node
node
internode
current (nA)
current (nA)
air gaps
R
2
0
-2
0
1
2 ms
current
across the myelin
• Function of myelinated nerve
Conduction velocity in a large myelinated axon is
around 50 ms-1.
An action potential at a single point lasts close to
0.5 milliseconds at body temperature.
Therefore the action potential is around 25 mm
(an inch) long.
If there are nodes at 1 mm intervals, over 20 will be
involved simultaneously in propagating a single impulse.
• Function of myelinated nerve
(real thing!!)
A
stimulator
membrane potential (mV)
B
DAP
+40
action potential
In the mammal repolarization occurs
without K+ channel involvement
(shown by Chu et al 1979)
depolarizing afterpotential (DAP)
-80
5 ms
H1
(cartoons only)
from Barrett EF and Barrett JN (1982)
• Function of myelinated nerve
• S.Y. Chiu, J.M. Ritchie, R.B. Rogart and D. Stagg, 1979
Why worry about the DAP – just a
detail isn’t it??
• DAP is functionally important because a myelinated axon
is easier to stimulate during the residual depolarization
(following the refractory period). The DAP contributes to
repetitive firing and sensory coding
• What is the process that allows repolarization of a node
following an action potential? This has been a puzzle
because kinetically fast delayed rectifier K+ channels are
not found at adult mammalian nodes of Ranvier.
Problem solved by Barrett and Barrett 1982 – DAP is a
part of the answer.
• Turns out if you know how the DAP is generated –you
understand how the axon works.
Explain what electrical capacity is!!
+
C
-
R
Explain what electrical capacity is!!
V
+
C
-
R
t = RC
time
Explain what electrical capacity is!!
t = RC
V
+
time
C
-
initially behaves like a closed circuit,
current flow determined by value of the resistor
I
R
finally behaves like an open circuit,
there is no current flow in the circuit at all
time
What is the potential drop across the capacitor when it has fully
charged, and the current in the circuit has dropped to zero?
• Biological membranes provide large capacities
(microscopic lipid bilayer with conducting
solution on either side) usually taken to be
1mFcm-2.
• Internodal membrane provides a capacity about
1000 times more than a node of Ranvier, so this
will short-circuit the action currents close to the
nodes, unless steps are taken to prevent it.
100 pF capacitor
(p pico, 10-12 ; SI nomenclature)
In parallel, what is the total capacty?
In series, what is the total capacty?
Myelin
low capacitance1/Ctotal = 1/C1+1/C2 +…. 1/Cn
Barrett and Barrett
resistance, makes myelin
a poor insulator because
there are current pathways
across it. Without it, the node
couldn’t repolarize, and the
axon would not have a
resting potential
Axolemma
large capacitance
Myelin
Periaxonal space
Axolemma
• Myelin provides a low capacity sheath – membrane
stack has a much reduced capacity (like separating the
two plates of a capacitor)
• The single internodal axon membrane (under the myelin)
has a high capacity, so that action currents go straight
through it – as though invisible, generating only a small
change in potential across the membrane, the DAP
• If the myelin were a good insulator the axon simply
wouldn’t work, because it would not have a resting
potential, and the action potential at the node couldn’t
repolarize!!!
• Function of myelinated nerve
getting the model right
Numerical simulation run at room temperature, Baker 2000
Barrett and Barrett (1982) got the model right
Summary of function
• Myelinated nerve is a remarkable structure
designed to efficiently propagate impulses at
high speed.
• Ion channels and other proteins are targeted to
discreet regions of axonal membrane in the
formation of nodes and internodes.
• Only nodes are electrically excitable.
• The myelin sheath provides low internodal
capacitance to allow energy efficient
transmission, but is a relatively poor insulator,
allowing internodal K+ channels to set the axonal
membrane potential.
Structure of myelinated nerve
• Learning Objectives (all knowledge
based):
• Be able to describe the basic structure of
myelinated nerve.
• Be aware of the distribution of ion
channels and cell-adhesion molecules that
helps define distinct domains along an
axon, and stabilizes the sheath
• In the PNS Schwann cells engulph axons, and
where the axon is greater than 1-2 mm in
diameter, the Schwann cell forms a myelin
sheath around it. Axons are ensheathed
sequentially by single Schwann cells.
• Schwann cells produce basement membrane
that includes laminin a matrix protein that is
essential for normal nerve development, function
and regeneration.
From Poliak and Peles 2003
Oligodendrocyte
Astrocyte foot process
In the central nervous system,
oligodendrocytes ensheathe
several axons. Axons as small
as 0.2 mm in diameter are
myelinated. Oligo’s can produce
Myelin that spirals in oposite
directions
Astrocytic foot processes
contact nodes.
Construction of myelinated nerve
Myelinating cells cause
clustering of Na+ and K+
channels
and induce large
axonal diameters
Rudolf Martini
10 mM
rat optic nerve
Formation of nodes of Ranvier
by Schwann cells
Peter Shrager
Na+ channels (green) Caspr 1 (red)
Fast K+ channels (blue)
Matthew Rasband
and Peter Shrager 2000
b-subunits interact with both intracellular and
extracellular proteins, controlling Na+ channel
localization and contributing to the control of
channel density
Oligodendrocyte
Ig-CAMs
tenascin-R
contactin
Nf186
b2
(lectin-like
domains)
b1
a-subunit
Axon membrane
ankyrin-G
spectrin,
actin cytoskeleton
b1 is crucial
McEwen j. Biol Chem 279: 16044-16049 (2004)
Glial CAMs recruit
axonal CAMs at
points of contact
Axonal CAMs
are attachment
sites for cytoskeletal proteins
D.P. Schafer and
M. N. Rasband (2006)
Figure 10.
Arroyo, E. J. et al. J. Neurosci. 2002;22:1726-1737
Copyright ©2002 Society for Neuroscience
• Myelin structure
Myelin protein P0 is a cell adhesion molecule in
Schwann cells
extracellular
membranes
EM of compact myelin
interpretation
Scherer and Arroyo 2002
Summary of structure
• Myelinating cells in CNS and PNS differ
• Axon-satellite cell interaction is crucial for the formation
of nodes of Ranvier e.g interaction of gliomedin in
Schwann cells and NF186 is an important factor in Na+
channel clustering
• Myelinated axon membrane incorporates domains
typically expressing certain ion channels and cell
adhesion molecules (CAMs)
• Sheath contains characteristic CAMs eg P0, and these
stabilize myelin
References
Structure of myelinated nerve eg:
L. Shapiro et al (1996) Neuron 17: 435-449 (crystal structure of P0)
M. Rasband and P. Shrager (2000) Ion channel sequestration in central nervous system
axons. J Physiol. 525:63-73.
E.J. Arroyo et al. (2002) Genetic dismyelination alters nodal structure J. Neurosci.
22:1726-1737
Y. Eshed et al. (2005) Neuron 47: 215-229 Giomedin mediates Schwann cell-axon
interaction and the assembly of nodes of Ranvier
Scherer and Arroyo (2002) Recent progress on the molecular organization of myelinated
axons J Peripher Nerv Syst. 7:1-12 (Review)
Poliak and Peles (2003) The local differentiation of myelinated axons at nodes of Ranvier.
Nat Rev Neurosci. 4:968-80 (Review)
D.P. Schafer and M.N. Rasband (2006) Current opinion in Neurobiology 16: 508-514.
(Review) READ THIS
References
Function of myelinated nerve eg:
Try: M.D. Baker (2000) Trends in Neuroscience 23: 514-519
Chiu SY, Ritchie JM, Rogart RB and Stagg D (1979) A quantitative
description of membrane currents in rabbit myelinated nerve. J
Physiol. Jul;292:149-66
Barrett EF and Barrett JN (1982) Intracellular recording from vertebrate
myelinated axons: mechanism of the depolarizing afterpotential. J
Physiol. 1982 Feb;323:117-44.