Propagating Down the Axon
From Lettvin
So, how does a pulse propagate down an axon undetected from the outside?
Tubulin A and Tubulin B monomers form an extremely regular chain deeply buried in the actin cytoskeleton that extends through the length of the neuron from end-to-end (said that before). The Tubulin chain has negative charges placed at precisely regular intervals. Between these negative charges are paired charge atoms organized into the molecular structure of the Tubulin monomers. As with actin, water tends to "stack" over these paired charges (polar association) and form a gel. The unpaired negative charge forces local water to stand up like iron filings on a magnet, forming a significantly harder mesh than the organized water.
However, nature does not like unpaired charges. Usually some ion, most likely K+ will associate with the unpaired Tubulin charge, cancelling the local electric field (somewhat) leading to an apparently fully polar surface to the Tubulin, whereupon all water stacks until these stacks compete with stacks from other polar surfaces.
Now come the dynamics.
The actin gel is liquified by the loss of Ca++ or the introduction of heat or mechanical force.
Na+ rushes down the gel to where the Tubulin strands are coursing by on their way through the cell.
When the Na+ reaches the Tubulin, it breaks even the radially hardened water around the charge sites.
The Na+ cancels the local charge and water begins to stack reestablishing the gel over the canceled Tubulin charge and trapping the Na+ in a shell of hydration.
A K+ ion can penetrate the gel because it exchanges water from its shell of hydration with organized water with very little energy gap.
Since the K+ ion associates more easily with the Tubulin than Na+, the latter is kicked off the negative site and has to find somewhere to go.
If there is a neighboring free site along the Tubulin what if there is none, the Na+ <!and its shell of hydration?> is pushed through the organized water gel to a new Tubulin site.
As the Na+ rushes into the actin gel, it cancels the electric field of the actin polymer and the K+ that was in high supply diffuses out., leaving K+ in low supply.
The change in proportion of Na+ to K+ in the Tubulin causes it to lose charge cancelling K+ as the Na+ increases. So the unstable Na+ Tubulin association is quasi-stable until the actin begins to gel again, kicking out the Na+ and K+ begins to form its unnaturally high concentration again.
This unnaturally high K+ is what kicks the Na+ off the Tubulin site, but with nowhere to go, it must move longitudinally.
It is prevented from moving backwards because there is always slightly less Na+ Tubulin charge canceling in front of it than there is K+ Tubulin charge canceling in back.
Thus a bolus of Na+ slips like a sleeve down the Tubulin polymer chain in whatever direction it is predisposed to go due to the paired positive/negative excitation I described in an earlier chat/email.
The dendrite is given a paired opposing excitation, a bolus of Na+ is formed, it is pulled down the Tubulin by electric field due to disparate association forces, it propagates through the cell body (not all neurons are like that, i.e. spinal cord has cell bodies off to one side), hits the denser gel of the axon hillock and is stopped dead. However, this stopping transfers energy to the gel which softens.
If multiple Tubulins deliver a bolus of Na+ to the hillock, the softening reaches a critical point and subsequent boli are no longer stopped. For a brief period of time, Na+ passes through the hillock and proceeds down the axon. After they have passed the hillock reforms its overdense gel and stops subsequent boli. I do not believe in "pulse generation" by the hillock. I believe in passive yielding to coincident boli.
The boli that make it through continue down the axon. One Tubulin is available for each side of every bifurcation of the axon.
The Tubulin carries its bolus sleeve all the way down to the synaptic bouton where the Na+ is released into the synapse, changing its ionic population. The synapse responds by increasing its rate of neurotransmitter release, relative to its reuptake rate. The neurotransmitter released into the cleft is held in the cleft by walls surrounding the cleft.
While in the cleft, neurotransmitter causes target cell proteins to either bind or release Ca++. Binding causes excitation, releasing causes inhibition. Either way, the target cell produces Nitric Oxide which diffuses rapidly in all directions, increasing the rate of reuptake of neurotransmitter, effectively shutting down the signal generated by the bolus by negative feedback. The synapse slowly recovers by coming to an equilibrium balance of neurotransmitter in the cleft versus neurotransmitter kept within the bouton in vesicles.
So, for an "irritable" cell (one that generates a pulse), the target cell always experiences a transient because its own feedback shuts off arriving signal immediately after arrival.
Jonathan: I believe I have "closed the loop" from excitation/inhibition pairing as Ca++ binding/unbinding to the generation of the bolus to its propagation through the cell to its coincident aggregation at the hillock to the propagation down the axon to its effect on the relative rate of output/input of neurotransmitter affecting the Ca++ binding/unbinding.
