Hi everyone, welcome to 10 minute neuroscience. In this installment, I’ll be talking about action potentials, the electrical impulses that travel down neurons and cause the release of neurotransmitters. Action potentials are a critical part of neural communication and essential to the function of the nervous system. An action potential is an electrical impulse, and to understand how it occurs it’s important to first understand the electrical properties of a neuron at rest, when it’s not firing an action potential. A neuron, like any other cell in the body, is surrounded by a cell membrane that separates the intracellular environment from the extracellular environment. The intracellular and extracellular spaces are each filled with fluid, and suspended in that fluid are charged particles called ions. These ions play an important role in creating the conditions that are just right for an action potential to occur, and there are a couple we need to pay special attention to: positively charged sodium ions, which are found at greater concentrations outside the neuron and are represented by these circles with Na+ inside them, and positively charged potassium ions, which are found at greater concentrations inside the neuron and are represented by the circles with K+ inside them. This unequal distribution of ions is maintained in multiple ways. First, the membrane of the cell doesn’t allow ions to easily pass across it. Instead, they need to travel through tubelike pores that span the membrane. These pores are called ion channels. Many ion channels are specific for certain ions. There are, for example, ion channels that allow potassium to cross the cell membrane, and other ion channels that allow sodium to cross the cell membrane. Additionally, some ion channels stay open all the time, while others open only in response to specific stimuli or signals, such as the binding of a neurotransmitter to a receptor. The channels that stay open all the time are sometimes called leak channels. Neurons have a large number of potassium leak channels, and relatively few sodium leak channels. Because of this, potassium is able to cross the membrane of a typical neuron relatively freely, but sodium can’t. This will be important to determining how potassium and sodium get distributed inside and outside the neuron, but we also have to consider a few other factors. The first is a protein called the sodium-potassium pump. The sodium-potassium pump is an enzyme that continuously pumps sodium ions out of the cell and potassium ions into the cell. It pumps two potassium ions in for every three sodium ions it pumps out. Thus, the pump helps to maintain a higher concentration of potassium ions inside the cell, and a higher concentration of sodium ions outside the cell. In addition to the sodium-potassium pump, we have to consider the influence of diffusion and electrostatic forces. Diffusion is the movement of a substance–in this example the movement of ions–from areas of high concentration to areas of low concentration. Electrostatic forces cause like-charged particles to repel one another and opposite charges to attract one another. So, positively-charged ions will be less likely to move closer to other positively-charged ions, but more likely to move towards a negatively charged ion or a negatively charged environment. So we have this situation where the sodium-potassium pump causes an accumulation of potassium ions inside the cell and a build-up of sodium ions outside the cell. Some potassium ions leave the cell through leak channels, and they move out of the cell because they’re moving from an area of high concentration to an area of low concentration. But eventually this tendency to diffuse out of the cell is balanced out by electrostatic forces, because as the positively-charged potassium ions leave the cell, the inside of the cell becomes more negatively charged than the outside, and that negative charge attracts the positively-charged potassium ions, keeping them from leaving. And so at this point, we’ve reached an equilibrium, where the effects of diffusion and electrostatic forces are balanced out. There is more potassium inside the cell and there's more sodium outside, and there’s a difference in electrical charge between the inside and the outside of the cell. Specifically, the inside of the cell is more negatively charged than the outside, and we call this difference of electrical charge a membrane potential. For a neuron at rest (meaning it’s not firing an action potential), its resting membrane potential is typically about -70 millivolts, although the exact number depends on the type of neuron we’re talking about. A membrane potential of -70 millivolts means the inside of the cell is about 70 millivolts more negative than the outside. Now, the stage is set for the action potential. We’ll use this figure here to look at how the membrane potential changes over the course of the action potential. So the x axis is representing time in milliseconds, and the y axis is representing membrane potential in millivolts. We’re starting at resting membrane potential, -70 millivolts, and the first step leading to an action potential is when the membrane potential moves closer to 0, becoming less negative, a process known as depolarization. When we have a separation of charges, we call that polarization, so depolarization is when that separation is reduced. Depolarization can occur, for example, when neurotransmitters bind to receptors and cause positively charged ions to flow into the neuron. This influx of positively charged ions will cause the inside of the neuron to become less negative, depolarizing it. These small changes in membrane potential caused by neurotransmitter binding and the resultant flow of ions into the neuron are called postsynaptic potentials. The neuron sums together these changes in membrane potential, and if the resultant depolarization reaches a certain point, which we refer to as threshold, then an action potential will fire. The action potential starts because when the neuron is depolarized to threshold, there are sodium ion channels that open. These ion channels open in response to changes in membrane potential, or changes in voltage. They’re called voltage-gated ion channels. Now remember we said there are typically more positively-charged sodium ions outside the cell and the inside of the cell is negatively charged with respect to the outside. So when these sodium channels open up, it will cause positively charged sodium ions to rush into the cell due to the influence of diffusion and electrostatic forces. This influx of sodium ions will depolarize the cell even further, and this further depolarization causes more voltage-gated sodium channels to open, leading to even more depolarization. This rapid change in membrane potential is sometimes referred to as the rising phase of the action potential. Before you know it, the membrane potential actually becomes positive and it shoots up to somewhere around positive 40 millivolts. This inrush of positively-charged sodium ions is the electrical signal that forms the basis for the action potential, and the signal will move down this long extension of the neuron called the axon. We’ll talk about how that happens in a moment, but first I want to explain how the action potential comes to an end. When the neuron’s membrane potential has reached its peak, the voltage-gated sodium channels begin to close. During the rising phase of the action potential, there are also voltage-gated potassium channels that open. These channels, along with normal potassium leak channels, allow potassium to rush out of the cell because now potassium is trying to move away from the positively-charged interior of the cell. This potassium moving out of the cell helps to repolarize the neuron, or move it back to its resting membrane potential, at which point voltage-gated potassium channels start to close. The whole process, from depolarization to repolarization typically only takes a couple of milliseconds—that’s thousandths of a second, so it’s incredibly fast. The sodium-potassium pump I mentioned earlier also helps to restore the balance of sodium and potassium inside and outside the cell. So, this influx of sodium ions is really responsible for causing the action potential, but what causes it to move down the axon? When this process of depolarization occurs in one segment of the axon, it happens in the segment right next to it as well because the adjacent segment is also rich in voltage-gated sodium channels, so the depolarization causes them to open and this regenerates the action potential in the next segment of the axon. So the action potential is kind of like a spreading fire that moves down the axon. Many of the axons in the nervous system are also covered in an insulating material called myelin represented by this striped structure here. Myelin is a lipid-rich material that 's wrapped around the axons of neurons, and it makes the propagation of action potentials down the axon faster and more efficient. One way it does this is by preventing current from leaking out of the axon, but the main way myelin increases speed of propagation is that it’s interrupted by these areas called nodes of Ranvier, where there are gaps in the myelin. The nodes of Ranvier are rich in voltage-gated sodium channels, so when a depolarizing action potential reaches a node of Ranvier, it causes another inrushing of sodium and a regeneration of the action potential. This causes an action potential to be regenerated at each node of Ranvier, propelling the action potential down the axon. This regeneration of an action potential at the nodes of Ranvier and slowing at the myelinated regions between them (which are called internodes) causes the action potential to appear as if it’s jumping down the axon, and we call this process saltatory conduction, from the Latin saltere, which means to jump. So now I’ve described the generation of the action potential and how it’s propagated down the axon, but it’s also important to mention that for a brief period after the initiation of the action potential, voltage-gated sodium channels become unresponsive and can’t be activated. We call this period the absolute refractory period, because a neuron will not be able to fire another action potential during this phase. Additionally, when the neuron is repolarizing due to the flowing of potassium out of the neuron, the potassium channels close gradually and allow enough potassium to flow out of the neuron that it briefly becomes hyperpolarized, which means the membrane potential is further away from zero than it was when it started out. This combined with the gradual transitioning of sodium channels back to an active state creates the relative refractory period, a time when a neuron will need very strong stimulation to produce another action potential since it’s now further away from threshold. One effect of these refractory periods is that they make the rate of action potential firing related to the intensity of stimulation. Action potentials don’t vary in size based on the intensity of a stimulus—they either fire or they don’t, and when they do they’re of a consistent amplitude or size; this principle is known as the all-or-none law. But more intense stimuli will cause more frequent firing of action potentials because they’ll be able to overcome the relative refractory period in neurons. But even with the roadblocks put into place by the refractory periods, neurons can fire many action potentials (sometimes hundreds or even more) per second. And that’s a summary of action potentials. Thanks for watching!