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Monday, February 14, 2011

A Piece of the ACTION (Potential)

Sorry for the brief hiatus, I had to participate in a major review of research projects last week, and it required travel. All seems to have gone well, and we can resume discussion of How the Brain Works. For this week, topics include Action Potentials: how neurons make and harness electricity; "Your Brain is Steampunk" and then a look at the mailbag.

Figure 1
The following is taken from my lectures to medical and graduate students. The artwork is mine, I'll not excuse it, but it also can't be blamed on anyone else. I have simplified, but I hope not too much to encapsulate this material enough for an informed public audience. For a humorous view, take a look at http://abstrusegoose.com/strips/rube_goldberg_large.PNG. Thanks to Eeyore for pointing this out to me when it was published. It is a very accurate depiction with the punchline "(oversimplified)".

Let's first start with a depiction of the neuron membrane (Figure 1). I recall a great Star Trek alien that refered to humans as "Great ugly bags of mostly water." It's true, and neurons are no different. Each neuron has a thin membrane of lipids (fats) and proteins that enclose a salt solution. The chemical composition of the salt solutions are different inside and outside the neuron as shown at right. The plus (+) and minus (-) signs indicate the "charge" of the ions, and it does not quite even out, allowing the inside of the neuron to have a slight negative charge. Note the detail in the left of the Figure 1 that says – these ions do *not* naturally cross the neuron membrane. They have to have channels.

The critical component of the solution for our discussion right now is sodium, Na+. Yes, too much sodium in the diet is a bad thing, but sodium is an essential chemical in the body. You will notice the concentrations are listed as "mM". That's "millimolar." One "molar" concentration is 35 grams of sodium per liter of water, or 4.72 ounces per gallon. "Milli" means 1/1000, therefore, 145 millimolar sodium is 0.145 x 4.72 = 0.56 ounces per gallon of water. You could *barely* taste that concentration of salt in water, so it really isn't much, and most people consume enough salt in the foods they eat and water they drink without the need to add salt for *nutritional* purposes. For flavor is another story.
Figure 2

So, sodium has a higher concentration outside the neuron than in, and it has an electrical charge. We can calculate the resulting electrical "potential" voltage simply by asking how much electrical energy would be required to prevent the positive charged sodium from entering the neuron and *balance* the concentrations at the same level as if no diffusion were possible (see Figure 2 at left).

Figure 3
We do know what this value is, and can calculate it as shown in Figure 3 at right. The equation uses R – the Gas constant, T – temperature (in degrees Kelvin), F – faraday's constant (to account for the charge of the ion), "ln" – the natural logarithm function, and the concentrations of sodium inside and out (the square brackets are chemist shorthand for "concentration of". This is called the "Nernst Equation" and we abbreviate it as "E" to indicate that it is the voltage at which the concentration is at "Electrical Equilibrium."

However, the most important part is that (A) sodium has to flow through a channel to get into the neuron, (B) that channel is normally closed. Thus when we *do* open the channel, we can get 66 millivolts worth of electrical energy out of this neuron (ionic current) by allowing the sodium ions to diffuse until they reach equal concentrations on both sides of the neuron membrane.

That's the complicated part – chemically. Now for the electrical part.

Figure 4
The way to open these sodium channels is with a slight positive electrical charge. We call that "depolarization." When a channel is depolarized, it allows sodium ions into the cell. The extra positive ion in the cell causes the electrical charge across the membrane to become more positive (usually it sits at about -70 millivolts). This extra positive charge also does a couple of other things, it diffuses out into the neuron, it attracts the negatively charged ions away from the inside of the membrane, and it causes the channel to shut itself off (Figure 4 at the left). Once the sodium ion stops flowing, the neuron can reset everything by allowing other positive charge ions to flow, and by pumping the sodium back out of the cell.

Figure 5
All of these stages happen in sequence, and the sequence causes a distinct electrical current to be recorded outside the neuron (Figure 5, right). We call this the "action potential" and it has a very characteristic shape – show this to any Electrophysiologist or Neuroscientist, and they can immediately tell you that it is a neural action potential. The very small depolarization caused by sodium entering through a single channel is enough to "depolarize" adjacent channels and make them go through the same process. Those channels in turn trigger other channels, and so on until we run out of neuron. What makes all of this work is that these channels are exceedingly small. A square centimeter or inch of neural membrane would contain millions of sodium channels, and they are especially concentrated in the "axon" – the part of the neuron that connects to other neurons and conducts information in the form of electrical pulses. Our last diagram, Figure 6 (left), shows a typical neuron, with the long (in some cases, meters long) axon. In this case, the electrical pulse has traveled halfway down the axon. Sodium ions are entering at the red arrows. AS sodium diffuses *down* the axon, it will eventually depolarize the membrane and open the sodium channels at the blue arrow. "Upstream" from the action potential, at the red arrows. The channels are closed and the neuron is pumping ions back to their normal concentrations.
Figure 6

The whole process takes about 2 to 5 milliseconds, and the neuron is ready to "fire" again. Action potentials travel at about 10 meters per second. That's maybe 25 miles per hour, although the *really* long neurons are specially insulated to speed that up 10 times or faster. Yes, signals from the brain to hands and feet travel at over 250 mph! And they do it over and over and over again – as much as 100 times per second, every minute, every hour, every day.

That's an amazing system, and it is all biologically based. The *information* content comes from changing the timing, the frequency, and the specific connections between neurons in a complex pattern not unlike the way a laser show makes complex patterns out of a single beam of light that simply turns off and on very fast.

Sound familiar? Kind of like a computer making information out of just ones and zeros? Well, perhaps, but that's a matter for the next blog.

1 comment:

  1. For some reason the link didn't work but when I found it on the Web again, this did:

    http://abstrusegoose.com/strips/rube_goldberg_large.PNG

    And then there is where it was originally published:

    http://abstrusegoose.com/306

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