Asger Hee Stjernholm, MSc

April 5, 2019

How Do Nerve Cells Work and Which Role Do They Play for Migraine?

The basics

The brain consists of about 100 billion nerve cells, each with a diameter of less than a tenth of a millimeter. Every one of these nerve cells is connected to about a thousand of its neighbors, making up a huge network with more than 100 trillion connections. This makes the human brain the most complex known object in the universe.
In order to think, act, sense and move, it is necessary for the brain to send thousands of electrical signals between nerve cells every second. Just like a cell phone can’t send a text message if the battery is dead, the brain also needs access to energy in order to be able to send signals. Nerve cells get their energy from burning glucose (“blood sugar”) from food together with oxygen from the inspired air. Compared to other organs, the brain needs a very large supply of energy: even though it only weighs about 2% of the total body weight it uses 25% of the oxygen we breathe.

In order to keep up with this large energy need, the brain has many and large blood vessels that (if everything is going according to plan) supply it with the necessary amounts of oxygen and blood sugar.

The structure of the nerve cells

Every nerve cell in the brain’s network looks like a small tree, with a central root, a root network, a long thin trunk and a small tree crown:

The root network consists of dendrites. These are thin branches of the cell that connect to other nerve cells and receive signals from them. When a signal is received, it moves through the dendrite to the cell body (the large central root in the picture). If the cell body receives enough and/or strong enough signals through its dendrites, it will produce its own outgoing signal that is sent out through its axon (the long slim trunk of the nerve cell). The axon ends in nerve endings (the small “tree crown” at the top of the picture) that are in very close contact with the dendrites of neighboring nerve cells. The narrow space between the nerve ending and the neighboring dendrite is called the synapse. When a signal arrives at the nerve ending, specific molecules called neurotransmitters are released into the synapse. The neurotransmitters quickly spread across the synapse and reach the neighboring nerve cell’s dendrites. When that happens, a new signal is triggered in the neighboring nerve cell, which can in turn trigger signals in other nerve cells. The nerve cells are in this way connected in a giant network somewhat like a computer.

The cell membrane

Every nerve cell is full of cellular fluid that is separated from the surrounding extracellular fluid (ECF) by a thin cell membrane. To understand the function of the cell membrane, the nerve cell can be visualized as a paint-filled can sitting in a bathtub full of water:

Just like the can’s walls and lid make it possible to keep the bright blue paint separate from the water, the cell membrane makes it possible to have a higher concentration of a certain molecule within the cell than outside it. If in the bath tub example the can’s lid is removed, the bright blue paint will spread out into the water until the water has an even, light blue color, in which case the concentration of paint has become the same within the can and outside it.

In the same way, without the cell membrane all concentrations within and outside of the nerve cell would become equal. If that happened the nerve cell would not be able to send any signals, since the energy for sending the signals actually comes from the differences in concentration in certain molecules between the inside and the outside of the cell. In this way the nerve cell is a lot like a battery: having a large difference in concentration between outside and inside is roughly the same as having a fully charged battery. This is necessary for the nerve cell to be able to send signals. If on the other hand the concentrations are the same inside and outside, this is the same as having a dead battery – in which case the nerve cell will not be able to send signals.

Potassium and sodium: the nerve cell’s battery

It is in particular the concentrations of two specific molecules that are important for the nerve cell to function: potassium (also known as K+) and sodium (also known as Na+). In the development of migraine attacks, the K+ concentration in the extracellular fluid play a large role. In a healthy, “fully charged” nerve cell, there is a lot of K+ inside the cell and very little outside it, while for Na+ it is the other way around – Na+ being plentiful outside the cell but very scarce inside it:

However, nerve cells are always a little bit ”leaky”, so there is always a little bit of K+ leaking out through the membrane, and a little bit of Na+ leaking in. Comparing again with a battery this is similar to a slightly damaged cell phone battery which is always losing a little bit of power, so that if you are not constantly keeping it plugged in the battery eventually goes flat. To make sure that nerve cells are always “charged” and ready to send signals, the cell membrane has a huge number of microscopic Na+/K+ “pumps”. These pumps are constantly pumping K+ into the cell and Na+ out of the cell. In this way, the pumps are continually charging the nerve cell, making up for the constant power leak through the membrane.

The reason that nerve cells need so much oxygen and blood sugar is that the pumps require a lot of energy to work properly – just like a cell phone charger needs to be plugged in to work.

Sending a nerve signal

The Na+/K+ pumps must work even harder after a nerve cell has sent a signal. The signal is sent by the cell by opening a lot of microscopic channels in the cell membrane, so that (instead of the little trickle of Na+ and K+ through the membrane) a lot of Na+ will suddenly flow into the cell and a lot of K+ will flow out. By in this way quickly releasing part of its electrical charge, the nerve cell releases enough energy to send a signal from the cell body through the axon to the neighboring cells.

After the nerve signal has been sent the channels quickly close again, but the concentration of Na+ inside the cell has by that time increased a lot (because a lot of Na+ has had time to flow into the cell) while the K+ concentration has decreased a lot, compared to the normal levels. Afterwards, the Na+/K+ pumps must therefore work hard to pump the extra Na+ out of the cell and pump the missing K+ out of the ECF and into the cells. Because of this hard work, the need for oxygen and blood sugar increases a lot because the pumps need a lot of energy to “recharge” the nerve cell.

Summing up

The nerve cells in the brain can both send and receive signals to and from neighboring nerve cells.

A nerve cell sends a signal by opening small channels in its cell walls, letting sodium flow in and potassium flow out.

In order to keep working, the nerve cell must continually recharge itself. This is done by pumping the sodium back out and the lost potassium back in, a process which a lot of energy.

Brain cells get their energy from the oxygen and blood sugar which is delivered to the brain by the blood.

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