4.0 Nerve terminal at a neuromuscular junction (nmj) or
endplate
The terminal region of a nerve facing a nmj is specialized to
convert an electrical signal to a chemical signal - release of
transmitter.
This is necessary because the electrical load faced by the
nerve
terminal - having to charge the enormous capacitance of the
muscle - is simply an impossible task! Not only is the muscle
diameter many fold larger (5-10) than the terminal but also
the
capacitance per unit area of the muscle is about 6 times the
normal 1ufd/cm^2.
Neuromuscular junctions in Frog
In an endplate region of a frog muscle, the myelinated nerve
innervating the junction looses its myelination and a few
terminal branches lie in troughs along the length of the
muscle.
These terminal branches are about 1 micron in diameter and
extend
for 200 - 300 microns in length. Katz and his colleagues have
shown that Na channels are present throughout most of the
length by Katz and his colleagues
of the terminal branches. At about 1 micron intervals along
the
length of the terminal branch are "active zones"- specialized
regions where transmitter is released into clefts in the
muscle
which house a high density of transmitter receptors.
Neuromuscular junctions in Lizard
Neuromuscular junctions in the lizard (Anolis carolinensis) are
compact plaques (about 25 - 30 microns in diameter)
of branching axons frequently bulging into boutons .
Lindgren & Moore,
Walrond and Reece This
morphology is similar in to that found in mammals (e.g. mouse:
Mallart ref). Here it has been found that the high Na channel
density in the heminode (the junction of the end of
myelination and the beginning of the branching bare axons)
decays rapidly with distance and are replaced by a high
density of K channels. When the K channels are blocked, an
"L" type of Ca channel is revealed. Clark Lindgren and I
developed a program in NEURON 2.0 (DOS version) to simulate
the voltage and current distribution which we observed there.
The assignment of morphology
and channel densities was shown in "Professional Style"
along with the resulting simulations of terminal ionic
currents.
Because this is such an important problem and offers a
great deal of insight into the relationships between
morphology, ionic channel types and densities, and function,
I have reprogrammed this simulation for NEURON 3.0 as an example
of a Digital Neuron.
Nature solves the problem of heavy Electrical Loading
Of particular interest is the recurring problem of the
high electrical (capacitive) load of the terminal faced by
the last nodes which must generate an impulse there in
order for Calcium current to enter and cause transmitter
release. This has been solved by having the last few nodes closer
together than the normal 1 - 2 mM. In the microscope, one can
see that the last node is no more than 50 microns from the
endplate and this length has been has been used in the
simulation. Furthermore, although I lack specific data, I have
gradually increased the internodal length up to the normal value
over the course of the next few myelinated internodes because:
- there is "tight coupling" between neighboring nodes (that is
their potentials change in near synchrony) and
- in order for the impulse to invade the terminal,it is
necessary to have more than a single internodal length shorter
than normal.
(You can see that this is necessary by increasing the last
internodal length to 1 micron and seeing the failure of the
impulse to invade the terminal.)
Once the internodal lengths have been set to that invasion of
the
terminal can occur, there is almost no attenuation in the
amplitude of the impulse as it moves throughout the terminal -
despite the presence of K channels and
the absence of Na channels!
The experimental data required for apriori assignment of channel
densities was not available but assignments were arrived at by
manual iteration to optoimze the fit, simultaneously, 5 current
traces. I used the constraint of smooth changes in channel
densities rather than
abrupt because:
- it seems reasonable to assume that here, as elsewhere,
"nature abhors high derivatives",
- that the stringent requirement of an abrupt change would be
more difficult for genetic control, and
- that step changes in density really were not necessary to
match the experimental data.
The currents flowing through these ionic channels can be seen in
the current graph. You should change the channel density
assignments and see how the currents you observe change not only
in the segment in which you have made the change but also
elsewhere. This is, of course, the consequence of current loops
(e.g. Na current entering at the heminode must flow out elsewhere
over the rest of the terminal: the converse is true for the K
currents flowing out at the ends of the terminals).