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: (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:

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).