Crash Course Nervous System 2: How Action Potentials Work

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Action Potential via Crash Course


Post 2 in the Crash Course series on how the nervous system works: Action Potential!

Neurons are extraordinary cells. Beyond being intricately branched and gigantic relative to most cells, every second hundreds of billions of electrical impulses called action potentials are transmitted in your body. Before we check out how that works, it’s useful to refresh a few electricity terms.

Voltage is a difference in electrical charge. In neurons, voltage is measured in milivolts (1/1000th of a volt) and is called membrane potential. The greater the charge difference, the greater the membrane potential. Current is the flow of electricity. In neurons, currents refer to the flow of positive or negative ions across cell membranes. But before we get to the flow of current, let’s understand the default or “resting state” of a neuron:

Neuron Resting Potential, crash course, resting potential, eyewire
Neuron Resting Potential via Crash Course


Your body is separated from the outside world by skin. This allows the internal state of your body to have different conditions than the outside world. Neurons have their own “skin” in the form of a cell membrane. It has ion gates – macromolecules made of many proteins – that change shape when specific molecules are present, allowing other specific ions (charged particles) to pass through the cell membrane. The movement of these ions changes the charge of the cell, causing a cascade of activity.

When neurons are at rest and not receiving electrical signal. their internal charge is negative thanks to the activity of a remarkable macromolecular machine: the sodium-potassium pump. This trans-membrane protein actively pumps sodium ions across their concentration gradient to the outside of the cell.

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Sodium potassium pump maintains an electrochemical gradient inside neurons (shown in teal). The purple molecule at bottom right is ATP, providing energy to activate the pump. For every two positively charged potassium ions (blue) it pumps in, it pumps out three positively charged potassium ions (red), making it more positively charged outside the neuron. Via Crash Course


In addition to sodium potassium pumps, neurons have many types of ion channels.

An Ion Channel via Crash Course
Ion Channel via Crash Course


Ion channels allow many charged ions to pass across a cell membrane. As charged particles rapidly diffuse across the membrane, they depolarize it, thus changing its charge.

Here are a few different types of ion gates:

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The most common ion channels are voltage gated. They open at certain membrane potential thresholds. Via crash course


ligand and mechanically gated ion channels, ion channels, action potential, molecules, eyewire, crash course
Other ion channels include Ligand gates (red), activated by neurotransmitters such as acetylcholine, and Mechanical gates (yellow), activated by physical stretching. via Crash Course


How an Action Potential Works

When all these gates are closed, a neuron is at rest. It’s polarized with a static membrane potential voltage of -70 mV .

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Resting state membrane potential via Crash Course


But say a stimuli hits a neuron, triggering an ion channel to open. As ions pass into the cell (much faster than shown below), they alter the membrane’s charge. Watch the white line to the right. It rises as voltage approaches a very important threshold: -55 mV.

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It’s all about getting to -55 mV. Sodium ions (red) enter neuron. Via Crash Course


Why -55 mV? At this threshold, thousands of voltage gated sodium channels open. A flood of positively charged sodium ions enter the cell and it becomes rapidly positively charged or depolarized. But this change in charge won’t last long.

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Sodium gates (purple) let forth a flood of positive sodium ions (red) into the neuron, resulting in depolarization. Via Crash Course


As a neuron reaches an internal charge of around +30 mV, a conformational shape change happens in the sodium channels. They close and voltage gated potassium channels open, allowing positively charged potassium ions to leave the cell.

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Membrane repolarization. Sodium channels (light purple) close. Potassium channels (dark purple) open and diffuse positively charged ions out of the cell. via Crash Course


This drops the internal charge of the neuron briefly below its resting state of -70 mV, activating the sodium potassium pumps to finish the job and bring the neuron to a maintained homeostasis. The entire process lasts 1-2 ms (1/1000th of a second).

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Action potential moves through a neuron branch. Via Crash Course


In this manner, action potentials propagate down neuron branches as chain reactions, causing a wave of depolarizations and repolarizations. Action potentials only travel in one direction.

So an action potential is moving along a branch when suddenly it reaches the end, the point of no return: a synapse.

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via Crash Course


A number of things can happen when an action potential reaches a synapse. To keep it simple, let’s consider the case of a chemical synapse, the type of junction that uses neurotransmitters.

Action potentials here activate local voltage gated calcium channels, releasing a flow of positive ions into the cell. The calcium causes sack like structures full of neurotransmitters called vesicles to release their contents into the synaptic cleft, the area between two neurons.

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An action potential reaches the end of the line: a chemical synapse. Via Crash Course


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Neurotransmitters are released from vesicles into the synaptic cleft, a region less than five millionths of a centimeter wide. They bind to receptor sites on the postsynaptic cell, triggering either excitation or inhibition. Via Crash Course


There are many types of neurotransmitters. Some are excitatory; others are inhibitory.

neurotransmitters, crash course

Here’s how excitatory and inhibitory neurotransmitters differ when it comes to the electrodynamics of neurons (see post 1 for a refresher on membrane potential). All images by Crash Course:

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Inhibitory neurotransmitters push neurons farther away from their threshold for having an action potential (hyperpolarization), making it harder for them to fire. Via Crash Course
excitatory neurotransmitters, crash course, action potential, eyewire, neuroscience
Excitatory neurotransmitters bring neurons closer to their threshold for having an action potential (depolarizing them), making it easier for them to fire. Via Crash Course


It’s neither a single synapse nor a single neurotransmitter that matters. There are over one hundred different types of neurotransmitters and over 100 trillion synapses in your brain. A single neuron can have thousands or even tens of thousands of synapses. As Hank Green points out in this video, “the likelihood of a postsynaptic neuron developing an action potential depends on the sum of the excitation and inhibition in an area.” This is commonly called constructive signal summation and is illustrated by EyeWire’s first scientific discovery (Nature 2014).

A few more Action Potential Factoids

Immediately following an action potential, neurons have a refractory period, a brief bit of time where they are not responsive to further stimuli. If another stimuli reaches a neuron during this period, it will not cause an action potential, no matter how strong the incoming signal is. This results in action potentials only propagating in one direction.

Neurons have consistent voltage thresholds: -55 mV activation, ~+30 mV repolarization. They vary their signals then not by Voltage (amplitude) but by frequency and speed (conduction velocity).

Weaker stimuli tend to produce slower, lower frequency signals while stronger or more intense stimuli tend to produce  more rapid, higher frequency signals.

Myelinated (insulated) neurons, such as are found in white matter and the peripheral nervous system, send the fastest signals.

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Myelinated action potential travels oh so fast because it effectively “leaps” from one myelin gap (nodes of ranvier) to the next. Via Crash Course


In the central nervous system, Myelin is produced by cells called Oligodendrocytes, which wrap around axons.

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Oligodendrocyte merrily making myelin sheaths. Via Crash Course



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