But mah beefy boys!
It’s hot.
For folks with MS, heat is a problem. But the problem should be much worse. In fact our neurons are so skilled that they give us the opportunity, the time, to function better than we really should. The reason is a series of little heroes in our nervous system, a plucky rebellion, a charming and daring group of rogues who break all the rules to keep the lights on. When we meet these heroes, we’re going to learn just how much of a wild and fantastic ecosystem a single nerve really is.
Nerves communicate electrically. At the site of the previous nerve a group of chargy chaps, sodium ions, communicate a signal to the gap at the end of the nerve known as a synapse. Chemical base jumpers are released and fly fearlessly across the gap to arrive at the start of the next nerve.
When they arrive at the next nerve they trigger that nerve to open the doors to the venue like it’s a good nightclub. Outside, chargy chaps are far more numerous than they are inside and because each of these chargy chaps are positively charged, and the nerve inside is negatively charged, they fly in through those open doors. Once inside they bring their charge with them. The other doors in the nerve open with electrical charge, they’re charge-gated, and so the chargy chaps trigger nearby doors to open, letting more inside. This forms a kind of charged wave of electrical energy down a long insulated corridor.
The corridor’s insulation has some gaps in, called the nodes of Ranvier, so the corridor features doors right at the start of these gaps designed to let chargy chaps in at the point where the insulation is weakest to ensure that the charged signal can get past it. The wave continues all the way down the corridor to the wingsuit warriors waiting at the end.
The trouble is that now the corridor is full of chargy chaps and, also problematically, full of their charge. If the nerve isn’t negatively charged when the next wingsuit warriors arrive, the doors will open but chargy chaps won’t flood in and trigger the impulse.
In step potassium pirates. These ladies are also positively charged and when the charge inside the corridor is too high generally, they stream out via their own little doors and take some of the charge with them. This restores the negative electrical charge of the nerve quite quickly ready for the next wingsuit warriors to arrive.
There are still too many chargy chaps lingering in the corridor. The impulse having travelled down the nerve there’s no reason for them to hang around and cause trouble, so the nerve gets the bouncers, ATPase pumps, also known as beefy boys, to boot them out. These beefy boys get to work pushing our chargy chaps out of the cell, and retrieving the potassium pirates. For every unit of energy a beefy boy can slowly kick three chargy chaps out and bring two potassium pirates back in, returning chemical balance to the nerve over time.
The beefy boys are constantly working out, seeing gains, and so they’re constantly eating. Chicken, protein powder, raw eggs, these folks don’t mess around. They need ATP. So the nerve recruits cooking crews to help, also known as mitochondria. The cooking crews get to work powering the beefy boys, so that they can deal with the rowdy chargy chaps, go find the missing potassium pirates, and everything continues to work well.
Wingsuit divers arrive and sodium chargy chaps enter. The sudden influx of charge causes charge-gated doors to open, bringing in more chargy chaps and conducting the electrical charge down the nerve. When the impulse has passed, potassium pirates leave to keep each section of the nerve electrically negative ready for the next impulse, and then the beefy boys put down their weights and get to work slowly throwing the chargy chaps out and letting the potassium pirates back in, grabbing food from local cooking crews so they don’t get tired, and ensuring the whole nerve is chemically balanced. Simple.
But then MS strikes. The immune system attacks the myelin surrounding the nerve, damaging the insulation surrounding the floors and walls in great sections of this important corridor. This exposes a lot of little doors that potassium pirates use to escape. Now we have a problem, as the chargy chaps enter potassium pirates begin to leave through these exposed doors and they take their charge with them. The next set of doors through which chargy chaps would enter are charge-gated and the loss of potassium pirates risks those doors failing to open. So the nerve builds new doors along the dodgy section of corridor. These doors open in sequence, letting more chargy chaps in to communicate the wave of electrical charge past the damaged section. The signal moves a bit slower than usual, but still gets there in the end.
This is a revolutionary bit of neurology. The signal should fail. By rights the electrical signal shouldn’t make it past the damage, but the nerve compensates by creating new sodium channels, new doors to let more chargy chaps in, to push that signal past the damage. And thus do we retain greater function than we otherwise would, owing to this little critical skill that nerves have to accommodate the damage.
But now we are left with a new problem, more doors means more chargy chaps wandering around the cell. If there are too many chargy chaps then the nerve risks remaining chemically imbalanced and that’ll cause its own problems. So the beefy boys get to work with greater fervor. They throw the chargy chaps out of the cell in greater numbers as quickly as they can, go find as many potassium pirates in the ether as they can. But this means they’re going to get hungrier, so the nerve buys in more cooking crews to serve them enough food. These boys eat a loooot so soon enough the entire corridor is filled with cooking crews baking bread, whisking eggs, boiling pasta, to feed the ever hungrier beefy boys.
This works but things are starting to get a bit tricky. Usually there’s plenty of electrical signal, so there’s slack in the system, but now the signal is weaker, closer to failure. If the nerve gets at all hot, the corridor doors can open and close inefficiently and usually that’s not a problem, the strong signal can accommodate some inefficiency, but when there’s damage and things are already tricky, a little inefficiency can create a lot of problems. If you can’t get enough chargy chaps in quickly enough to compensate for the loss of potassium pirates, then the signal can fail to get those charge-gated doors to open and will stop there and then.
Enter calcium. These are remodelling renegades, signalling cells to release chemicals, alter proteins, and to remodel the structure of the cell. When these girls get into the cell they pick up tools and go to work remodelling the corridor. They’re important, skilled, but the nerve only lets a tiny number in at a time because these ladies will get a bit overzealous, will decide that they totally see what’s wrong with this corridor, and will all go to work breaking things down if too many of them get into the cell at once.
The nerve has sodium/calcium exchanges, known as the turnstyles of terror, which allow a few extra chargy chaps in and in exchange pull a few remodelling renegades back out when needed. This is how the nerve usually keeps the remodelling renegades in check. But the corridor now already has a bunch of new doors letting in a load of new chargy chaps and the chemical balance that allows this exchange is off. Worse, the beefy boys are doing their work pushing chargy chaps back out but there are so many chaps to expel, they’re working hard enough that they’re getting really hungry and the cooking crews have already filled the corridor and they still can only barely keep up with demand.
Now, while the cell is functioning, things are on more of a knife-edge. With the cooking crews working to capacity and beefy boys still hungry kicking out chargy chaps, it wouldn’t take much for things to start to go awry.
Eventually things go wrong. The cooking crews can’t serve the ever increasing demand from the beefy boys for protein and whey and whatever else they’re eating. The corridor is already full of cooking crews and there’s no way to satisfy the needs of the boys. So they start to get tired. They get sluggish and then can’t keep up with the influx of chargy chaps. Too many chargy chaps risks the turnstyles of terror being unable to keep the calcium at bay.
The signal risks failing.
When the chargy chaps are too numerous eventually the turnstyles of terror begin to flow in reverse, allowing chargy chaps to leave in greater numbers and temporarily restoring function. But this allows the remodelling renegades to enter the corridor. They pick up tools and get to work, deconstructing the corridor. They start to remodel the cooking crew stations, who struggle ever more to serve the needs of the beefy boys, who can’t keep up with the chargy chap influx.
A vicious cycle has begun.
Eventually the remodelling causes the skeleton of the corridor to begin to break down. The skeleton of the nerve crumbling, ultimately the corridor falls apart and everyone inside is hurtled out into brain space.
The nerve has died.
This is a pretty terrifying eventuality. But there are drugs in the works that might help out. Fampridine has just been approved for use on the NHS. Fampridine is a potassium channel blocker, it keeps more of those smaller doors closed, ensuring that the potassium pirates don’t escape into brainspace in too great numbers. It doesn’t solve every problem, but it might help with one of them.
So the next time that someone looks at you skeptically about the heat and your intolerance of it, remind them of your nervous system heroes. If all else fails wave your arms in the air and shout ‘but mah beefy boys!’ and then get another ice cream from the freezer.