Transcript Document

LECTURE 12: MYELIN AND SALTATORY CONDUCTION
REQUIRED READING: Kandel text, Pgs 22, 81-87
Myelin is an electrical insulator sheath wrapped around axons
Oligodendrocytes produce myelin on CNS axons
Schwann cells produce myelin on PNS axons
Short gaps in myelin along axons called nodes of Ranvier
Myelin’s function is to speed action potential propagation down long axons
MYELIN SHEATH COMPOSED OF MANY LOOPS OF A GLIAL PROCESS
Each oligodendrocyte has several
processes, each of which produces
a myelin sheath on a different axon
Schwann cells each form only a
single myelin sheath
MYELIN SHEATH GENERATED BY CONTINUED MIGRATION
OF PROCESS LEADING EDGE AROUND AXON
While the leading glial process continues to encircle the axon,
the earlier-formed loops undergo compaction
to form the compact myelin sheath
MYELINATED FIBERS VIEWED IN CROSS-SECTION
Low magnification
Light microscopy
Electron microscopy at
very high magnification
reveals alternating
major dense lines and
intraperiod lines
High magnification
electron microsopy
ORGANIZATION OF THE MYELIN REPEAT PERIOD
PLP is the most abundant protein in CNS myelin
P0 is the most abundant protein in PNS myelin
THE PARANODE IS SITE OF TIGHT AXON-GLIAL ADHESIONS
ROLE OF MYELIN IN FAST ELECTRICAL TRANSMISSION
Unmyelinated
Axon
(SLOW CONDUCTION)
Myelinated
Axon
(FAST CONDUCTION)
SODIUM CHANNELS ONLY AT NODES
AT VERY HIGH DENSITY
Action potential at one point along unmyelinated axon produces current that only
propagates short distance along axon, since current is diverted through channels
in axon membrane. So action potential can only next occur short distance away
Myelin reduces effective conductance and capacitance of
internodal axon membrane. (how???)
Action potential at node of Ranvier produces current that propagates
0.5-5 mm to next node of Ranvier, generating next action potential
THIN AXO-GLIAL SPACE AT PARANODE LOOPS CREATES HIGH
NODE-INTERNODE PERIAXONAL RESISTANCE WHICH
ELECTRICALLY ISOLATES INTERNODAL MEMBRANE
SINCE
Rparanode >>>> Raxial & Rleak
CHARGING OF
INTERNODAL
MEMBRANE
VERY SLOW
AND CHANGE
IN INTERNODE
VM IS
INSIGNIFICANT
NODE
Only 20 Angstrom gap between
mature paranodal loop
and axonal membrane
Rparanode
Rparanode
Raxial
PARANODE
Tight junctions between
mature loops
Raxial
INTERNODE
PARANODE
NODE
POTASSIUM CHANNEL SHUNT NOT REQUIRED IN
MOST MATURE MYELINATED AXONS
Myelinated axons conduct action potentials at ~ 50 mm/msec
Total refractory period of nodal sodium channels after inactivation
is ~ 5 msec.
Therefore, by the time sodium channels return to rest after an action potential,
the spike has propagated 25 cm away
(which is terminated in most cases)
Potassium channel inhibition in mature myelinated fibers
does not alter conduction or promote misfiring.
FORMATION OF NODAL, PARANODAL, AND JUXTANODAL
PROTEIN CLUSTERS DURING MYELINATION
Kv1
Kv1
Sodium channels cluster early at wide immature nodes. As nodes narrow and
mature, sodium channel density increases.
Potassium channels cluster later and shift their position. They first appear at nodes,
but move to paranode and then juxtaparanode as structure matures.
POTASSIUM CHANNELS ARE OF CONTINUED IMPORTANCE DURING MATURATION OF MYELIN,
SINCE ONLY FULLY MATURE FIBERS CONDUCT FAST ENOUGH TO MAKE THEM UNNEEDED.
PERSISTENCE OF POTASSIUM CHANNELS IN MATURE JUXTAPARANODES MAY FUNCTIONALLY
PROTECT FIBERS IN CASE OF PARTIAL DE-MYELINATION
MUTATIONS CAN CAUSE MINOR OR MAJOR MYELIN LOSS
“SHIVERER” mutant mouse has almost
complete absence of myelination,
due to a failure of precursor cells
to differentiate into oligodendrocytes
Other mutations which impair
myelination are mutations in the
major protein components of
the myelin sheath
MUTATIONS IN PLP GENE CAUSING HYPOMYELINATION IN CNS
Similarly, structural mutations in PNS myelin protein genes
cause defective myelination of the PNS