Neurons, Explained in Ten Minutes
Find out what are dendrites, axons, ion channels and action potentials.
Every tissue of the body is formed by specialized cells. For example, muscles are formed by muscle fibers or myocytes, which are able to contract, generating force and movement. The liver has hepatocytes, cells specialized in processing and storing food. The kidney has brush border cells and other types of cells. And so forth.
The nervous system has two main types of specialized cells: neurons and glia.
Neurons are the most specialized cells in the body. Their main property is their ability to transmit signals as electrical waves in their membranes. The only other cells able to do this are the myocytes of the muscles. Neurons make contact with other neurons called synapses, where the information carried by the electrical waves is conveyed by special substances: the neurotransmitters.
Neurons have a distinct shape that looks like a tree. The branches of the tree are called dendrites (which, indeed, comes from the Greek word for branch). The dendrites converge in the body of the neurons, or soma. From it emerges the trunk of the tree called the axon. Typically, neurons have only one axon, but it may divide into several down the way.
Most axons are enveloped by thick layers of a fatty substance called myelin, in short stretches that leave small spaces between them, the nodes of Ranvier.
Axons ends in synapses that connect the neuron with the dendrites of other neurons.
Information flows in a neuron from the synapses to the dendrites, converging in the body and then flowing out to the axon. In some cases, the information travels backwards: from the axon to the body or from the body to the dendrites and the synapses. However, this is just to aid the normal flow of information.
In the axon, information travels in the form of electrical waves called action potentials. You may think that electricity flows along the axon like it does on an electric cable: back and forth. Or that it forms electric pulses, like information is sent in the cable of your speakers or headphones. However, what happens is quite different: the electric current flows perpendicularly to the axon, and not along it, forming an electric wave, the action potential. It is that wave what moves down the axon.
But to explain the action potential, I first need to explain what are ion channels.
Ion channels are pretty much what this name indicates: proteins that sit across the cell membrane with a tiny tube in their core. That tube opens sometimes, lettings some particular ions flow across the membrane, either from the outside to the inside of the cell, or the other way around.
But what are ions?
Table salt is sodium chloride, a molecule formed by positively charged sodium ions, Na+, and negatively charged chloride ions, Cl-. Positively charged ions are called cations, and negatively charged ions are called anions. Negative charges and positive charges attract each other so, in a salt crystal, the sodium and chloride ions sit next to each other forming a network. However, when you dissolve salt in water, the sodium and chloride ions get separated and enveloped by molecules of water.
Just like in sea water, there is a lot of sodium chloride in our blood and in the cerebrospinal fluid that bathes nerve tissue. There is also a smaller amount of calcium chloride. Whereas sodium, Na+, has only one positive charge, calcium , Ca2+, has two positive charges. This is very important for cells, which use calcium to carry signals in their interior.
The other important ion for cell function is potassium, K+. Like sodium, potassium only has one positive charge, but it is larger in size.
This difference in size between sodium and potassium allows ion channels to differentiate between these cations. Therefore, there are sodium channels and potassium channels. There are also calcium channels, which use the two charges of Ca2+ to distinguish them from the other cations.
Ion channels are normally closed. They open for very short times, measured in milliseconds (a thousandth of a second). There is an arm of the protein that swivels into the channel, stopping the flow of ions and out of the way when the channel open.
Since ion channels are molecules, their opening and closing are quantum events that follow the probabilistic laws of quantum mechanics.
Ions channels are classified according to what opens them:
Ligand-gated ion channels open when a neurotransmitter binds to them, acting like a key that opens the door of the channel.
Voltage-gated ion channels open when there is a change in the membrane potential. A part of the protein that forms the channel acts as a sensor that moves when there is a change in the voltage, opening the channel. There are ten voltage-dependent sodium channels, termed Nav1.1 through Nav1.10. Nav1.7 channels are important for pain; people born without them do not experience pain. Voltage-gated calcium channels were initially classified as L, N, P/Q, R and T, but now they have been renamed Cav1.1 - Cav1.4 (L), Cav2.2 (N), Cav 2.1 (P/Q), Cav2.3 (R) and Cav3.1 - Cav3.3 (T). L-Type calcium channels are important in muscles and the heart. N-Type calcium channels are important for neurotransmitter release in synapses.
Ion channels gated by sensory signals, like temperature or pressure, include proteins like the capsaicin receptor (TRPV1), the menthol receptor (TRPM8), and TRPA1, the receptor responsible for the spiciness of horseradish and wasabi. They are all channels permeable to Na+ and Ca2+. TRP channels are present in nerve terminals in our skin, where they act as temperature sensors. Other ion channels are sensitive to pressure. They that are responsible for initiating sensations of pain, itch and tact.
Some venoms and drugs produce their effects by binding inside ions channels, plugging them. They are called channel blockers. For example, tetrodotoxin (TTX) is one of the most potent known venoms, responsible for the deadly bite the blue-ringed octopus and the toxicity of puffer fish (fugu). It is a blocker of voltage-dependent sodium channels. So is saxitoxin, produced by dinoflagellates, a type of plankton that is responsible for seafood poisoning.
Local anesthetics, like the lidocaine and bupivacaine used by your dentist to block sensation in your mouth, are also blockers of voltage-dependent sodium channels. They are not poisonous as tetrodotoxin and saxitoxin because they are much less potent.
Conotoxins are a variety of neurotoxins used by marine snails of the genus Conus to kill fish with their harpoons. Omega (ω) conotoxins are blockers of voltage-dependent calcium channels. One of them, ω-conotoxin MVIIA, has been developed as a potent pain inhibitor: zinocotide.
There are many blockers of potassium channels, including the scorpion toxins iberiotoxin and charybdotoxin, some conotoxins, and many medications.
The membrane potential
All cells in the body have an asymmetrical distribution of ions across their membrane. There is about 50 times more sodium on the outside, and 50 times more potassium on the inside. There is also more chloride on the outside, although this chloride gradient is reversed in some anomalous conditions. The gradient of calcium is much more dramatic: there is 10,000 times more calcium on the outside than in the inside of the cell.
This asymmetrical distribution of ions across the cell membrane creates an electrical voltage across it, called the membrane potential. You may think of the cell membrane as a battery with poles on the outside and the inside of the cell. The positive pole is outside the cell and the negative pole inside.
The value of the membrane potential in neurons is around -70 millivolts (mV). This is not much, considering that the electrical outlets in your house have an electrical potential of 110 volts (1,500 times higher). However, this is a lot of energy for the tiny axons, which are just 0.1 to 10 micrometers thick (a micrometer is a millionth of a meter).
Just like a battery, the membrane potential is used to store energy by all cells. However, neurons also use it to send signals and process information. When a cell dies, its membrane potential goes down to zero. Conversely, a collapse of the membrane potential causes the cell to die.
We can know if a cell is dead or alive by measuring its membrane potential. This is done using a technique called patch-clamp electrophysiology, in which tiny glass pipettes containing electrodes are attached tightly to the membrane using suction. The same technique is used to measure the opening and closing of single ion channels.
If the membrane potential stores energy, that energy has to be put there somehow. This is done by proteins called ion pumps. They use metabolic energy in the form of ATP molecules to move ions from one side to the other of the membrane.
The most important ion pump is the sodium/potassium pump (Na+/K+-ATPase), which moves 3 Na+ ions out and 2 K+ ions in across the membrane. In the process, it spends (cleaves into ADP and phosphate) one molecule of ATP. This keeps sodium ions out of the cell and potassium ions inside. It also results in the net movement of one positive charge to the outside of the cell, building up the membrane potential.
There are also calcium pumps that keep the calcium gradient.
Action potentials are waves of electrical current caused by the opening of ion channels. The electrical current is across the membrane, and can also be understood as a change in the membrane potential.
A depolarization is a decrease in the membrane potential. Voltage-gated sodium channels in the axon open when they sense a depolarization, letting sodium ions, Na+, into the axon. Since they have a positive charge, when Na+ ions travel to the inside of the axon they change the membrane potential from negative inside to positive inside. The battery at the membrane actually changes polarity, going from -70 mV to +40 mV.
There are also voltage-gated potassium channels in the axon that open when they sense this strong depolarization. Since there are more potassium ions, K+, inside the axon, they flow to the outside of the axon. This creates a current opposite to that of the sodium ions, which restores the membrane potential, even with a slight overshoot (hyperpolarization). At the same time, the voltage-gated sodium channels become desensitized and they close.
The voltage-gated sodium channels in the nearby part of the axon sense the strong depolarization of the action potential and they open, so the whole process repeats itself down the axon. The result is a wave of reversal of the membrane potential moving down the axon, which is the axon potential.
Since the segment of the axon where an action potential has just occurred is hyperpolarized (more negative than -70 mV) by the opening of potassium channels, sodium channels cannot open there. This has two consequences:
It forces the action potential to move in one direction, instead of traveling both ways in the axon.
It creates an interval of time when an action potential cannot occur in that segment of the axon, putting a limit to how close together two action potentials can be. In other words, there is a limit in the frequency of action potentials, which is different for different types of axons.
Saltatory conduction: the amazing jumping action potentials
Most axons are covered by coats of myelin, fatty envelops that leave between them gaps called nodes of Ranvier.
A membrane depolarization in one node of Ranvier is strong enough to trigger the opening of voltage-gated sodium channels in the next node of Ranvier. Hence, an action potential in a node of Ranvier triggers an action potential in the next node, causing action potentials to jump from one node of Ranvier to the next. This is called saltatory conduction.
Saltatory conduction has two advantages:
It reduces the amount of energy spent to send an action potential. Sodium ions that come into the axon with each action potential have to be moved back out by ion pumps, at the expense of metabolic energy. Without saltatory conduction, our nervous system would expend so much energy that we would not be able to afford our large brains.
Saltatory conduction increases the speed at which action potentials move down the axon, from about 1 meter per second (m/s) to up to 100 m/s. Without this speed, human brains would not be able to function.
Not all neurons have axons covered by myelin. C-fibers, which are the axons of many of the neurons that transmit pain, are unmyelinated. Since they cannot use saltatory conduction, they have slow conduction speeds, about 1 m/s. That means that the pain elicited at a distant area of your skin takes a good fraction of a second to get to your brain. Enough time that you can tell the difference between the moment that you feel the impact - a tactile sensation carried by myelinated A fibers - and the pain of the impact, carried by the C fibers.
Frequency and firing patterns of action potentials
A neuron doesn’t fire just one action potential, but many action potentials in rapid succession. The frequency and the pattern of this firing of actions potentials encodes the information that the neuron is sending to other neurons.
Frequency means that a neuron may fire from one action potential per second - 1 hertz (1 Hz) frequency - to 100 action potentials per second (100 Hz), or even more.
Pattern means that action potentials may be evenly spaced at a fixed frequency, or grouped in bursts of several action potentials at high frequency separated by intervals without action potentials.
One pattern of action potential important in the brain is the theta burst: a few action potentials at 100 Hz forming bursts separated by 0.2 seconds. This firing pattern stores memory in synapses in the form of synaptic plasticity. It also triggers the release of special neuropeptides like brain-derived neurotrophic factor (BDNF).
Dendrites are the many branches that converge into the cell body (soma) of the neuron. They are shorter and thicker that the axons. While axons have a uniform thickness, dendrites get wider as they approach the soma.
For a long time, it was believed that dendrites do not have action potentials. Later, scientists found that they do have them, although they are different from the action potentials of the axons: they are mediated by calcium ions and not just by sodium ions.
Still, the main means by which dendrites transmit information is through waves of depolarization in their membrane that are longer and less intense than the action potential. These depolarization waves start at the synapses as excitatory postsynaptic potentials (EPSPs). While action potentials are so strong that they reverse the membrane potential, EPSPs are merely decreases in the membrane potential, or waves of depolarization. And while action potentials have the same amplitude, EPSPs can be of different intensities. As they move down the dendrites, the EPSPs of different synapses add to each other, increasing in amplitude.
Some synapses are inhibitory, meaning that they generate inhibitory postsynaptic potentials (IPSPs) instead of EPSPs. IPSPs are waves of hyperpolarization, or increases in the membrane potential.
When an EPSPs encounters an IPSPs in the dendrite, the IPSPs decrease the size of the EPSP, sometimes canceling it altogether. This interplay between EPSPs and IPSPs in the dendrites and the body of the neurons is how the neuron processes information.
All these waves of membrane potential finally converge at the place where the axon begins (the axon hillock). If the depolarization is enough to open the voltage-dependent sodium channels there, then an action potential is fired. If it falls below this threshold, then nothing happens.
In reality, what happens is that large depolarizations at the axon hillock trigger multiple action potentials, whose frequency is proportional to the size of the depolarization. Smaller depolarizations trigger action potential firing at lower frequency. This way, information in the dendrites is encoded into the frequency of the action potentials.
The neuronal soma
The soma or body of the neuron contains the nucleus, the part of the cell where genetic information is stored in the DNA.
A neuron, just like any other cell, synthesizes its proteins by transcribing the genes in the DNA into messenger RNA (mRNA), which is then translated into proteins in the ribosomes. These are veritable nanomachines that read the genetic code in the mRNA and assemble amino acids, one by one, following a specific sequence to make a protein.
All the proteins that I mentioned before - ion channels, ion pumps, neurotransmitter receptors - plus all the enzymes and structural proteins of the neurons, are made this way.
An interesting problem is that each synapse builds its own proteins according to action potentials it receives from other neurons, independently of what is happening in the other dendrites and synapses of the same neuron. Then, how does the nucleus know what proteins it needs to make and where to send them?
As it turns out, many proteins are made at ribosomes placed next to each synapse, that capture mRNAs coming down the dendrite from the nucleus according to the signals received by that particular synapse. This makes possible for synapses to grow or shrink, a phenomenon called synaptic plasticity.
Synapses and synaptic plasticity deserve their own explanation. I will devote another article to that.