Post on 23-Dec-2015
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
10 mM Na+ 140 mM Na+
120 mM K+
2 mM K+
Inside Outside
K+ channels
Na+ channel
10 mM Na+ 140 mM Na+
120 mM K+
2 mM K+
+ve
+ve
Inside Outside
-ve
Na+ channel
K+ channels
10 mM Na+ 140 mM Na+
120 mM K+
2 mM K+
Inside Outside
-80 mV
Na+ channel
K+ channels
10 mM Na+ 140 mM Na+
120 mM K+
2 mM K+
Inside Outside
-80 mV
Na+ channel
K+ channels
• 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 up-swing of action potential
Na+ channel inactivationand K+ channel activationunderlie repolarization
K+ channel activationgenerates afterhyperpolarization
Function of myelinated nerve
nerve conducts action potentials by local circuit currents
Function of myelinated nerve
node of Ranvier
internode
outside
inside
direction of impulse
optic nerve axons (Brady et al 1999)
compact myelin
Shiverer mouse(myelin basic protein null)
local circuit current
potentialsrecordedextracellularly
axon
longitudinal currents
transmembranecurrent
Tasaki 1959
air gaps
R R
nodesingle fibreteased out
current across the myelin
0 1 2 ms-2
0
2cu
rren
t (n
A)
transmembrane current at a node
0 1 2 ms -2
0
curr
ent
(nA
)
2
Function of myelinated nerve
internode
Tasaki 1959
air gaps
R R
nodesingle fibreteased out
current across the myelin
0 1 2 ms-2
0
2cu
rren
t (n
A)
transmembrane current at a node
0 1 2 ms -2
0
curr
ent
(nA
)
2
Function of myelinated nerve
inward current
outward current
internode
• 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.
-80
+40
me
mb
ran
e p
ote
ntia
l (m
V)
5 ms
stimulator
A
B
depolarizing afterpotential (DAP)
• Function of myelinated nerve
action potentialIn the mammal repolarization occurswithout K+ channel involvement (shown by Chu et al 1979)
H1
(cartoons only)
(real thing!!)
from Barrett EF and Barrett JN (1982)
DAP
• S.Y. Chiu, J.M. Ritchie, R.B. Rogart and D. Stagg, 1979
• Function of myelinated nerve
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!!
+
-
R
C
Explain what electrical capacity is!!
+
-C
R
+
-time
V = RC
Explain what electrical capacity is!!
+
-C
R
+
-time
V = RC
time
I
initially behaves like a closed circuit,current flow determined by value of the resistor
finally behaves like an open circuit, there is no current flow in the circuit at all
What is the potential drop across the capacitor when it has fullycharged, 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 1Fcm-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?
Axolemma
Periaxonal space
Myelin
Myelinlow capacitance-1/Ctotal = 1/C1+1/C2 +…. 1/Cn
Axolemma large capacitance
Barrett and Barrett resistance, makes myelina poor insulator because there are current pathways across it. Without it, the node couldn’t repolarize, and theaxon would not have a resting potential
• 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!!!
Numerical simulation run at room temperature, Baker 2000
getting the model right
• Function of myelinated nerve
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 m 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 m 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+
channelsand induce large axonal diameters
Na+ channels (green) Caspr 1 (red)Fast K+ channels (blue)
rat optic nerve
10 M
Matthew Rasband and Peter Shrager 2000
Rudolf Martini
Peter Shrager
Formation of nodes of Ranvierby Schwann cells
-subunits interact with both intracellular and extracellular proteins, controlling Na+ channel localization and contributing to the control of
channel density
1 is crucial
tenascin-R
ankyrin-G
Nf186contactin
1
2
Axon membrane
Oligodendrocyte
spectrin,actin cytoskeleton
Ig-CAMs
(lectin-likedomains)
-subunit
McEwen j. Biol Chem 279: 16044-16049 (2004)
D.P. Schafer and
M. N. Rasband (2006)
Glial CAMs recruitaxonal CAMs at points of contact
Axonal CAMsare attachment sites for cyto-skeletal proteins
Copyright ©2002 Society for Neuroscience
Arroyo, E. J. et al. J. Neurosci. 2002;22:1726-1737
Figure 10.
• Myelin structure
Myelin protein P0 is a cell adhesion molecule in Schwann cells
extracellular membranes
Scherer and Arroyo 2002
EM of compact myelin interpretation
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
ReferencesStructure 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.