Membrane Voltage and Electrical Signaling
This is post #5 of this series on the Brain (First Post and Last Post). As I mention every time, these posts are from a series of lectures by Prof. Jan Schnupp, and I want to make sure he is properly quoted and credited. Many parts are his lectures verbatim. However, for any errors, mistakes or inaccuracies in anything I write in here, I take all the credit. I probably misunderstood him or made it up. His course material is available here.
Summary
What do we know so far? We know we have almost 100 billion neurons in our brain, we know that they are little fat bubbles, they are fat bubbles that are filled with saltwater, there is saltwater all around them, they have tube-like structures growing out of them, they are called axons and dendrites.
Now, neurons are filled with saltwater and they are surrounded by saltwater, but the type of saltwater that is inside them is not the same type of saltwater as that which is outside them, and the reason for this is a protein, and there is actually a whole series of proteins that will basically make it their job to pump certain types of salt ions out of the cell and pump others in.
Sodium Potassium Pump
So, for example, all your neurons have a so-called sodium-potassium pump, which is a protein that will basically fold in a particular way to allow sodium ions, sort of cooking salt ions, to stick to it on the inside, and when they are stuck in there, it will flip over to let the sodium ions escape, and then it will wait for potassium ions to bind, and then it will flip back in and let the potassium ions in, and this is a process that is actually driven by your cell, it actually expends energy on pushing out sodium and sucking in the potassium, and the consequence of this is that the fluid outside your cells is very high in sodium, so this is why your tears are salty, because you have these pumps pumping sodium out and pumping potassium in.
There are similarly other pumps, the pumps that will allow sodium back in, in order to push calcium out. So calcium is very, very, very low inside your neurons.
Your neurons are high in potassium, low in sodium, low in calcium, and they are also low in chloride. Chloride also gets pushed out of the cells. So we have uneven distributions of different sort of ions here, so that sodium is low inside, high outside, chloride is low inside, high outside, calcium is very low inside, much higher outside, potassium very high inside and low outside. These particular values, if you are trained to be a medical doctor, you have to know them.
If you are not trained to be a medical doctor, at least not yet, you don't have to learn them, but you should, if you possibly can, remember that the fluid that bathes the cells of your body, including your brain, it is largely salt water solution.
Sodium and chloride in water, whereas there is much less sodium and much less chloride inside the cells. And inside the cells you get lots of potassium and lots of organic anions, the organic anions come from the proteins. So we have sodium chloride outside, potassium organic anions inside.
Now that's the status quo, and we have very little calcium.
Diffusion in neurons
That's the status quo, that's the way the cell normally is. But of course, the thing is, all of these sodium ions and the chloride ions and the potassium ions, they are constantly being bounced around by this water that kicks into them with all this sort of fervor that we talked about in previous posts. So if they get a chance, if the sodium ions get a chance to go in, or the potassium has a chance to escape, they will use that chance.
And the force that drives this is simply the diffusion that we explained earlier. So of course, normally they can't do this unless there are pores, unless there are channels through which they can go, but in fact there are channels. And the reason that there are channels creates a voltage, an electrical driving force across the membrane of the cell. If you were to stick a little electrode, and people can actually do this as an experiment, stick a little electrode inside a nerve cell, and you measure the voltage relative to the outside of the cell, you realize that there is actually a voltage, which really just means it is an uneven charge distribution.
Polarised neuron membrane
So then you get more positive charge on the outside of the cell, and more negative charge on the inside of the cell. Now of course, these positive charges will attract the negative charges, and this causes a tension that you can measure in volts. The voltage across its membranes is about 65, 70 millivolts or so, for the nerve cell at rest. Now 60 millivolts doesn't sound like much, and it isn't all that much, because if you buy a little battery, it will be 1.5 volts. That's substantially more than 60 millivolts. But you have to bear in mind that these 70 millivolts or so operate over a membrane that is only about 10 nanometers thick. The thing about electrostatic attraction between charges is that it obeys what physicists call the inverse square law.
Now that sounds very complicated, but ultimately it just means that the force is very strong if things are close together, and not so strong if they're further apart. The force changes with the square of the distance. If you've ever played with magnets, if they are far apart, really you don't feel much, but if you try and get them really close together, then the attractive force or the repellent force suddenly becomes very strong. This is sort of also due to the inverse square law of magnetic forces.
So similarly the electric forces, the positive and negative charges that are unevenly distributed across the cell can attract each other, can have a very strong attraction here. It corresponds to 7 million volts per meter electric field strength.
Now in air, an electric field strength of 3 million volts per meter is what it takes to cause lightning. So on the very small scales of the membranes of your brain cells, this piffling little 60 or 70 millivolts is a huge electric force, which if you happen to be just a tiny little protein that sits there, you will feel it.
It will bend you out of shape. So just by distributing charges differently across the membrane, we can do things on the very small scale that matters for neurons. So this was just to remind you about the electrostatic forces that really create this attraction and repulsion. So really what happens in a neuron at rest is that it will have a lot of potassium inside it, very little potassium outside it.
The potassium will want to diffuse out if it can. Now all your neurons in your brain will have little channels in them made out of protein that will allow potassium to leak out. This potassium will leak out, but of course potassium is positively charged. So we suddenly get a surplus of positive charge on the outside and negative charges from the organic alloys left behind.
Now there will be an electrostatic attraction, they will try and suck the potassium back in. So we've got two forces opposing each other, diffusion pushing it out, electrostatic attraction pushing it back in. And there will come a point, the so-called equilibrium potential, where on average you get as much potassium being expelled by diffusion as you get sucked back in by electrostatic attraction. That's what creates this electric tension across the membrane of the neuron at rest.
All neurons at rest have a charged, polarized membrane. This polarized state means the neuron is saying, "Okay, nothing's happening; this is my normal state." This polarization is due to the difference in ion concentrations inside and outside the neuron. When there's a lot of potassium inside the neuron and less outside, and if potassium starts to leak out through special channels in the membrane, it creates a voltage difference across the membrane. Even a small amount of potassium leaking out can generate a significant voltage because electrostatic forces are quite strong.
Physicists can calculate the exact voltage needed to reach equilibrium using complex formulas that involve gas constants, temperatures, and Faraday constants, but we don’t need to worry about that detail here. The key point is that if potassium leaks out, it creates a voltage across the membrane, but sodium, which is also positively charged and more abundant outside the cell, doesn’t usually move in because the neuron has a specific protein, called the potassium leakage channel, that only allows potassium to pass through. This channel lets potassium shed its hydration shell, pass through, and then gain a new hydration shell on the other side, but sodium can’t do this with the same channel.
Depolarisation
Under normal conditions, neurons are mostly permeable to potassium, allowing it to move in and out freely. However, under certain conditions, the neuron can become permeable to sodium, which means sodium can flow in. If sodium enters the neuron, it causes the voltage across the membrane to drop, or "depolarize." Depolarization is when the voltage across the membrane collapses, and this is actually the "excited" state of the neuron. So, the smaller the voltage difference, the more excited the neuron is.
Now, imagine you are a neuron. You're at rest with potassium inside and sodium outside, and your membrane is ready for action because it has channels that allow potassium to leave. When something happens, like if you’re a stretch receptor in the skin and someone pulls on you, this pull opens channels that let sodium rush in. The more you pull, the more sodium enters, causing the neuron to lose its polarization and become more depolarized. Your voltage goes from around -70 millivolts to -50, then -30, then -20, and so on. If sodium completely overtakes potassium, the inside of the neuron can even become positive relative to the outside.
This change in voltage helps neurons encode information about the world around them. If you’re a stretch receptor, the stronger the pull, the more depolarized you are. If you're a light receptor in the eye, you signal how bright or dark it is by how depolarized your membrane is. In the ear, sound pressure changes your polarization level. So, neurons use membrane voltages to represent information from the environment, which is like an analogue code—a continuous representation of real-world stimuli as changes in membrane voltage.
Let's break down how neurons represent the world around us. Neurons translate everything we sense into electrical signals called membrane voltages. These voltages then get processed and combined across various types of sensory inputs, like touch, sight, and sound. But for now, let's focus on the basics: the presence of physical or chemical signals is encoded as a change in the voltage across the neuron's membrane.
Representation of the world through membrane voltage
Imagine a neuron at rest. Potassium ions leak out, leaving the outside of the cell positively charged and the inside negatively charged. Now, if something like a stretch receptor (a type of sensory receptor) gets activated, it lets sodium ions in, creating a positive charge inside the cell. This positive charge is attracted to the negative charges nearby, and as a result, an electric current flows along the neuron's structure, called neurites. This current spreads the signal automatically through the neuron.
However, there's a catch: these signals don't travel very far on their own. They tend to leak out because the potassium channels, which help maintain the initial voltage, are still open. This leakage means that the electrical signal weakens quickly, over just a few millimeters. And that's a problem because some neurons in your body are very long—up to two meters, like those that run from your toes to your brain. So, to send signals over long distances, neurons need a trick.
This trick involves renewing the current along the way using special proteins called voltage-gated sodium channels. When a neuron's membrane is depolarized (its internal voltage becomes less negative), these channels open and let in more sodium ions, which further depolarizes the cell. This process repeats along the neuron, renewing the signal and allowing it to travel long distances without weakening.
The process is called an action potential, or nerve impulse. When these sodium channels open, we say the neuron "fires." Once the neuron fires, the action potential moves along the axon—the long, cable-like part of the neuron. But this is an all-or-nothing event: if the initial depolarization isn’t strong enough, no action potential occurs. If it is strong enough, the neuron fires, triggering a cascade of sodium channels opening along the axon.
After the sodium channels open, they quickly close again, and the neuron returns to its resting state, helped by potassium channels that open to push potassium ions out. This entire process takes about one millisecond, allowing a neuron to potentially fire up to a thousand times per second.
Neurons use these impulses to send information. However, the frequency of firing, or the rate at which these action potentials occur, is what encodes the information. A high firing rate might signal strong stimuli, while a lower rate might signal weaker stimuli. This is known as a rate code. But neurons can’t fire more than about 400 impulses per second on average, so they have to encode a lot of information with relatively few signals compared to modern technology like USB cables, which can handle much higher data rates.
Neuron impulse adaption
Now, one of the cool things about neurons is that they can also adapt. For instance, if you put your hands in cold water, your cold receptors initially fire rapidly. But if you keep your hands there, the firing rate slows down as the receptors adapt, making the cold feel less intense. This adaptation can cause various sensory effects, like afterimages when you look away from a bright light.
Neurons also have a protective layer called the myelin sheath, made of glial cells that wrap around the axon, providing insulation. This helps signals travel faster. Diseases like multiple sclerosis can damage this myelin sheath, causing problems with signal transmission, which can affect things like muscle control.
In summary, neurons represent the world by encoding information as changes in membrane voltage and sending signals through action potentials. They can adapt, have special structures like myelin for efficient signal transmission, and use complex mechanisms to ensure signals travel long distances effectively. This intricate system allows your brain to process and respond to the vast array of stimuli you encounter every second of your life.
Slides
Attached are some slides from Prof. Schnupp summarising all that we have learned so far.
