Botox

Disconnect of emotional display is a sign of schizophrenia (inappropriate affect) or too much Botox injected into the face. That plus a BlueTooth ear piece conversation and who can tell the difference?

Botox, yup, the same stuff they line up for at the cosmetologist, is a deadly poison from a group of bacteria that seems hell bent on churning out a stream of really nasty vile poisons. From tetanus with spine breaking convulsions to whole families dead from canned beans, this charming bacterial family turns off smiles in a variety of ways.

Think about it. A series of neurotoxins (way high in biologic complexity and differentiation) from muck? Single cells that eat the dead without need for oxygen? WHY?

The key thing is that these toxins are so utterly specific. There has to be energy and resources spent by the bacteria to make these complex toxins.

 

So what is a neurotransmitter? Basically a key. The actual chemistry of their atomic sub bits is almost irrelevant.  When a nerve signals the next nerve it releases a chemical that does nothing much but which does fit nicely into a receptacle on the other nerve - like a key that fits a lock. That's it.  Once in that other nerve's lock, the signal is passed and events in the other nerve take over.

As nerve cells act as computer logic, one signal does not hardly ever just make the next nerve fire off. A convergence of nerve endings have a cumulative effect. Some are stimulatory and, in a sense, agree that the next nerve should fire. Some are referees which tend to dampen activity, say maybe another action takes precedence. How would precedence be worked? By inhibiting things that might get in the way. So complex hierarchies of cell connections allow or disallow certain patterns of neural activity.

The voting is done chemically. Acetylcholine (ah-CET-tul KO-leen) is a very common signaling key that fits the locks of many receiving nerves. When acetylcholine lands on the right membrane endings that membrane is apt to trigger its own response. Apt to but that depends on how much stimulus is enough.

Well at the nerve to muscle junctions, there isn't much of a debate going on. Muscles don't think, they just do what they are told. So it isn't a surprise that nerve to muscle transmission may be all of one kind at any given nerve-muscle junction. Motor-nerve plate is the name usually used for that spot where nerve bosses muscle. Acetylcholine is the nerve's released triggering agent.

Nerve-AcCh750
Ooooo, look, a nerve ending spouting orders. See that vacuole (bleb opening on the surface)? It is releasing acetylcholine. No muscle can say no to that stuff.

Actually there are chemicals that CAN screw up the receiving side receptacle - the keyhole. Nicotine hypes it up and curare blocks it. Muscarine, from poison mushrooms can excite certain acetylcholine receptors in a non stop way, but be dislodged by atropine (the antidote). There is active paralysis by jamming the nerve signal in the on state - mushroom (muscarine) poisoning wherein the motors are stuck on. So pupils go narrow, spit drools everywhere, and the overlook is one of on-ness, rigid tense loss of control. Antidote atropine.

But the flaccid paralysis from no transmitter at all being release, floppy paralysis of botulism would be made worse by atropine . It's Goldilocks, too much, too little, and just right.

Absent those complications of chemical poisoning, how do you tell nerve endings, that are simply over signaling?, using a poison, to SHUT UP! Well if they are acetylcholine types then Botulinum toxins do that. Botox inside the nerve ending blocks the RELEASE of acetylcholine.

Nerve-AcChBotoxCut
Not to scale, obviously, the inside of the nerve ending is seen through a window. Three vacuoles are noted. The bright one is opened at the surface discharging acetylcholine. How does it know where to do that? How does it latch on? Well, depicted as a tail hanging off the other two intact vacuoles (just jam packed with acetylcholine) is a molecular structure that snags another attractive molecule on the end plate membrane inner surface. It will attach then help pull the bubble of neurotransmitter right up to the membrane until the two membranes (vacuole and end plate) merge. Without that latching on, the vacuole just floats around.

The Botulinum toxin (depicted as a reddish goober) has a portion of its molecule which recognizes the outside nerve membrane and very strongly bonds to it. Then the toxin molecule does a half gainer and winds up inside the nerve cell where the other part of that same molecule grabs on to that tail of the vacuole - like a pit bull - and that vacuole can no longer bond with the neural membrane and thus not release its payload.

So Botulinum toxin has to get into the nerves to work, but not into the blood stream where unintended functions may be affected. So it is injected into the target muscles inside of which are those nerve end plates. Diffusion and incredible tenacity of this toxin for its two targets does the rest.

    So THAT'S HOW BOTOX WORKS!

Actually, I don't think so.

OK in apathetic faces maybe. But when we see a kid with two spastic arms stuck high in the air, do we calculate the maximum allowed toxin dosage and  give one half to the right and the other half to the left arm muscles?

You could. But we see better results from giving all of it to one side, especially the most reactive side and only to the fastest muscle portion. It's that cross reaction thing again. And it is the spindle receptors themselves, the acceleration sensors that live in the muscle. They are made out of muscle and have their own nerve endings. Botox THEM and you hit the source of the high velocity over response reflexes. You quiet the internuncial pool by quieting the big players that feed that pool.

Paraspinal Botox for some very sick kids who had high poised arms and deadly eating issues (100%) was not given for reason of those findings. Yet both findings responded to the paraspinal injections as they share the same internuncial region. We could gauge the paraspinal Botox direct action by the arms and somewhat by easier feeding.

For this reason also target high velocity muscles rather than wasting toxin in large slow muscles. Yeah, the big ones are easier to inject and the skinny ones mean you actually have to know your anatomy. Sorry about that.