Video: Introduction to neuron electrophysiology

Neurons are the electrical superheroes of your body. They receive, integrate, generate, propagate, and transmit electrical signals to make your brain buzz and your muscles move. But here's the shocking truth: All this electrical ability hinges on tiny charged-up particles known as ions. These are the unsung heroes behind the scenes, driving the bioelectrical activity that keeps your neurons firing and your body and mind in motion.

In order to understand how these signals are generated, we will first need to describe the structure and function of the cell membrane of a neuron and its involvement in facilitating electrochemical events necessary for neuronal function.

Welcome along today as we introduce you to the fundamentals of neuron electrophysiology.

So, what do we mean by neuron electrophysiology? Well, it's all to do with the electrical properties of neurons, which we know are the primary cells of the nervous system. We're going to learn about what brings about these properties in the first place and what happens to the neuron when there are changes to these properties. Wrapping your head around these concepts will then help you to understand exactly how neurons receive, generate, conduct, and transmit signals, and how this all contributes to their functions and behaviors.

All cell types are electrically active, meaning they use electrical signals for various functions and they also all obey something called Ohm's law, which is defined as voltage equals current multiplied by resistance. In the case of the cell, the current refers to the flow or movement of charged particles called ions and the resistance or control of movement, in this case, is mostly related to the cell membrane.

It is these two things which are fundamentally responsible for the electrical properties of a neuron. Voltage simply refers to the force needed to move charged particles from one place to another and it is primarily caused by differences in concentrations of charged particles like ions inside and outside the cell, but we'll explore this more later in this tutorial.

So let's talk about ions.

Ions are atoms which have acquired a net electrical charge which can be either positive or negative. This results from an unequal amount of protons and electrons in their makeup. Positive ions are referred to as cations, and in the case of neurons, the cations we are usually talking about are potassium, sodium, and calcium. Negative ions are called anions like chloride.

Chemically, when ions are placed in a solution without any physical barriers separating them, they eventually become evenly distributed through simple diffusion, meaning their concentration across the solution reaches equilibrium.

Now we know that neurons, like all cells, have an outer boundary known as a cell membrane, which is responsible for controlling what passes between the intracellular and extracellular environments of the neuron.

The cell membrane comprises a phospholipid bilayer. These phospholipids have a hydrophilic polar head group and two hydrophobic hydrocarbon tails. Because of this arrangement, only gases, hydrophobic, or fat-dissolving molecules like steroids, and small polar molecules like water can cross the cell membrane. Larger molecules like proteins or sugars cannot passively cross the cell membrane. Similarly, charged particles like ions which are hydrophilic, or water-loving, cannot pass through the cell membrane without assistance.

So the presence of the cell membrane and the fact it's impermeable to ions means that the movement of ions through diffusion is not possible so we end up with different concentrations of ions inside and outside of the neuron.

In the case of a neuron, we can think of it like a salty banana, as there is a high concentration of salt, or sodium ions, on the outside versus a low concentration on the inside, and conversely, we have a high concentration of potassium ion on the inside of the neuron and a low concentration on the outside.

And when we have an uneven distribution of any ion like this, chemical concentration gradients come into play, which means that ions want to move from areas of high concentration to areas of low concentration until equilibrium is achieved. But now, since ions are also charged particles, which can either be positive or negative, we also need to keep in mind that opposite charges are attracted to one another so there also can be an electrical gradient at play here.

If we can assume that one side of a membrane is more positive and the other more negative, a positive ion wants to move towards negativity and a negative ion wants to move towards positivity until there is an equal distribution of positive and negatively charged ions on either side. And we're going to see shortly that both these chemical and electrical gradients can be combined to form an electrochemical gradient which contributes to the first electrophysiological property of neurons we'll learn about, which is known as membrane potential.

To be a little more specific, since neurons are a type of excitable cell, we're going to refer to this as resting membrane potential, meaning we're talking about differences in electrical charges inside and outside of the neuron when it's at rest, or not receiving or transmitting signals.

So let's have a look at our neuron and just focus on potassium for now.

Here we have the cell membrane of the neuron, and for now, let's assume that it is electrically neutral, meaning that the overall concentration of positively and negatively charged ions is equal on either side of the membrane. Let's now add a transmembrane protein known as an ion channel, which has a pore that selectively allows the passage of ions between the intra- and extracellular compartments. And since we're only talking about potassium for now, we'll only consider these as being permeable to potassium.

Since we know potassium exists in a higher concentration inside the cell than outside, this means that potassium will follow its concentration gradient from high to low concentrations, meaning potassium ions, which are positively charged, leave the cell.

So the inside of the cell membrane is becoming more negative relative to the outside due to the loss of positive potassium ions to the extracellular environment. In addition, as potassium ions move towards ion channels, other negatively charged molecules like proteins attempt to follow them as negative is attracted to positive. However, since the cell membrane is impermeable to these compounds, they become concentrated along the inside of the cell membrane.

So we end up with an increase of positive ions along the outside of the cell membrane and an aggregation of negatively charged compounds on the inside. This creates an electrical gradient. And remembering that opposite charges attract, this causes some potassium ions to get pulled back across the cell membrane into the cell, from more positive to less positive environments, so the opposite of direction of the chemical gradient.

These gradients, or forces, pulling potassium ions out and into the neuron will naturally become equal and cancel each other out, so there will be no net movement of ions when they are in electrochemical balance or equilibrium, meaning for every potassium ion which leaves the neuron along the chemical gradient, one is pulled back in along the electrical gradient. And it's at this point that we can define something known as the equilibrium potential of potassium, also known as the Nernst potential.

The equilibrium potential of potassium is around -90 millivolts, and if the cell membrane was only permeable to potassium, the membrane potential -- meaning the difference in electrical potential inside and outside of the neuron -- would also be -90 millivolts. However, in reality, the cell membrane of the neuron is also permeable to other ions.

So now let's add in another ion to the mix; this time, sodium.

Now remember that sodium ions are found in higher concentrations outside the cell relative to inside. So if ion channels for sodium are present, sodium will move into the cell, along its chemical gradient, thereby adding more positive charges to the intracellular environment. Like potassium, sodium also has its own equilibrium potential which is around 60 millivolts.

Taking the equilibrium potential of sodium and potassium ions into consideration now, if both are able to move across the cell membrane in equal amounts, the resting membrane potential would be somewhere halfway between the two values -- +60 and -90 millivolts. However, they are not much able to move in equal amounts. At rest, the cell membrane of a neuron is much more permeable to potassium than it is to sodium. In fact, there are around 40 times more potassium ions crossing the cell membrane than there are sodium ions, which also means that although some positive sodium ions are moving into the neuron, there are many more positive potassium ions leaving the cell.

This results in a resting membrane potential which will be closer to the equilibrium potential of potassium. And when we take into consideration the equilibrium potential of all ions crossing the cell membrane like calcium and chloride as well as their relative permeability, we end up with a resting membrane potential of around -70 millivolts. And when we have a membrane potential like this, which is not zero, we can describe this membrane as being polarized.

Now we have spoken a lot about how chemical and electrical gradients drive the movement of ions across the cell membrane, but also, there is one other factor which we need to take into consideration in regards to ion concentration, and this is active transport.

As we just saw, the membrane potential of the cell membrane is reliant on ion concentrations. If left over time, however, these concentrations would passively dissipate, which would lead to a gradual loss of the membrane potential.

To prevent this happening, enzymes known as sodium-potassium ATPases, commonly referred to as the sodium-potassium pump, work to replace sodium and potassium lost from the extra- and intracellular environments, respectively. Here, sodium and potassium ions are pumped against their concentration gradients using energy.

For every ATP molecule used by the pump, three sodium ions leave the cell and two potassium ions enter. And once again, we can see that more positive ions are leaving compared to those entering -- three going out and two coming in -- so this also contributes to the relative negativity of the intracellular environment. More importantly, however, the sodium-potassium pump maintains the overall chemical gradient needed to maintain a membrane potential.

So let's recap. We now know that the cell membrane of a neuron is polarized, meaning there are differences in electrical charge on either side of the cell membrane of a neuron which is primarily brought about by the concentration and movement of potassium and sodium ions. And it's these differences which define its resting membrane potential, which we found out has a value of around -70 millivolts.

Now we also know that neurons are a type of electrically excitable cell, meaning they are capable of generating and propagating electrical impulses -- and we're to learn in another tutorial on action potentials that it is changes in the membrane potential of the neuron which are responsible for this. But for the remainder of this tutorial, we will focus on the structures which facilitate changes in ion concentration and membrane potential, which are the ion channels.

Ion channels are made up from transmembrane subunits that assemble to form a pore and accessory structures. The number of these subunits varies across different subfamilies of ion channels. In general, ion channels have three main properties. Firstly, they are responsible for facilitated diffusion of ions. As we learned earlier, the phospholipid bilayer of the cell membrane actively inhibits the passage of charged molecules across the cell membrane. Ion channels enable ions to pass through them passively along their electrochemical gradients, without consuming energy.

In addition, the majority of the ion channels are highly selective, meaning they only allow specific ions to traverse through them.

Due to their unique protein structure, many types of ion channels maintain a closed state, which in turn prevents ions from passing through. However, in response to various stimuli, which can be of electrical, chemical, or mechanical nature, the structure of the channel can change, leading to the opening of the pore, allowing ions to pass through.

The structural changes ion channels undergo are linked to specific functional states. Ion channels can be categorized as being in an activated, closed, or an inactivated state. In the activated or open state, ions can pass through the channel. In the closed or resting state, no ions can pass through the channel. However, with the introduction of specific stimuli, it can be prompted to open and become activated. When ion channels are in the inactivated state, they do not permit ion passage, but they can also not be activated even when exposed to appropriate stimuli. The functional states of ion channels that we just discussed are regulated by various stimuli.

Ion channels can be categorized into four main different types, based on their activation or deactivation pattern and the specific stimuli they respond to.

Now let's have a closer look at each type. We will start off with leakage ion channels. These remain constantly open for ion passage while maintaining selectivity for different ions. We've already encountered leakage ion channels earlier in this tutorial when we looked at the sodium and potassium ion channels which contribute to the resting membrane potential of the cell membrane.

Next, we'll discuss ligand-gated ion channels. These channels are activated or deactivated by a ligand. Ligands are molecules which bind to a specific site known as a receptor and generally function as a signal to initiate a biological process. In the context of neurons, ligands can be a chemical substance, specifically a neurotransmitter, binding to a receptor on the ion channel. This binding induces the opening or closing of the ion channel's pore to allow select ions to travel through.

Next, we have voltage-gated ion channels. These channels respond to changes in the voltage difference across the cell membrane. Under normal circumstances, the resting membrane potential of the cell membrane is negative -- you'll remember that we said it's around -70 millivolts. When that voltage becomes less negative and reaches a value specific to the voltage-gated channel, known as a threshold, the ion channel opens and allows ions to cross the membrane.

Last, but not least, we have mechanically-gated ion channels. These channels open because of a physical distortion of the cell membrane of the neuron, which is either stretched or the cell's cytoskeleton is directly affected. This mechanical force induces a change in the structure of the channel, leading to the opening of its pore. These channels are particularly important in sensory neurons, which are responsible for detecting mechanical stimuli such as touch, sound, and changes in pressure.

And that concludes our tutorial for today.

We gave you a first glimpse into neuron electrophysiology and looked at how ions affect the electrical properties of the cell membrane. To revise this content, check out our quiz and other learning materials in our study unit on this topic.

See you next time.