How Does a Brain Cell Work

There are 100,000,000,000 nerve cells in a brain, surrounded by at least 10 times as many supporting cells...
25 November 2007


A neurone


They are found in well-organised groups; they communicate constantly through long ranging connections; there are one hundred billion - 100,000,000,000 - of them, surrounded by at least 10 times that many supporting non-neuronal cells, and they are all inside your head...

They are of course brain cells. Of course there are many different types of cell in the brain; most are concerned with protection and supportive functions like fighting disease and providing the necessary environment for the high maintenance nerve cells (also called neurones). We make sense of the world around us by the collective activity of these nerve cells and in turn they direct our response to that world; violent rage and philosophical insight both begin with nerve cells but how exactly do they work?

Nerve cells need a lot of energy

The essential job of nerve cells is to send and receive messages, a process that uses electricity and intermittent chemical signals. This electrical signalling requires constant pumping of electrical charges between the inside and outside of the nerve cells; to do this the brain uses a disproportionately large amount of energy compared to its size. The movement of electrical charges is performed by pumps or transporter proteins in the membrane of a cell and these are powered by the energy-rich molecule adenosine triphosphate (ATP) (see this link for a video of how a nerve cell works).

The purpose of all this pumping and transporting is to maintain large imbalances in the distribution of charged particles (ions) between the inside and outside of brain cells. Principally this involves keeping the levels of sodium and calcium inside the cell very low and keeping the level of potassium higher than the outside. In addition to producing large differences in concentration between inside and outside a cell, this distribution of ions causes an electrical potential difference - the inside of a brain cell is electrically negative by about, seventy thousandths of a volt (70 millivolts). It doesn't sound much, but when you take into account how thin is the cell membrane - 5 nanometres or 5 thousand millionths of a metre - this translates to an electrical potential gradient of 140,000 volts per centimetre! This is a very powerful electrical field and when combined with large differences in ion concentration, it acts as a powerful driving force to move ions across the cell membrane - but this can't happen until ion channels open.

What are ion channels....

Ion channels are proteins that sit in the cell membrane, the fatty layer that forms the boundary of a cell. They have a central pore, or channel, which allows ions to move between the inside and outside of the cell. Left to themselves these ions move from areas of high to lower concentration, and this is exactly what happens during the normal operation of brain cells.

Why study ion channels?

  • Malfunctioning ion channels are responsible for a large number of health disorders
  • Many drugs act on ion channels to produce their beneficial effects
  • This is particularly true for the nervous system. Tranquilizers, analgesics, anaesthetics and anti-epileptics are some examples of drugs which act directly on ion channels.
  • Anaesthetics open potassium channels,
  • anti-epileptic drugs modify sodium and calcium channel operation as well as some channels operated by inhibitory neurotransmitters.
  • Sodium and calcium channels are also targets of drugs used to improve heart function.
  • Stimulation of insulin release from the pancreas is caused by drugs which block potassium channels.
  • Epilepsy, muscular dystrophy, irregular heartbeat (long QT syndrome), cystic fibrosis, and some kidney ailments all result from inappropriate changes in the way ion channels work.

When ion channels open, charged particles flood across the membrane divide at a tremendous rate (several thousand each time the channel opens). This image conjures the idea of water flowing from the sluice of a dam, but it is more subtle than that. Instead, imagine a packet of vegetable soup with holes in it; some holes only allow peas to pass through whereas others are selective for carrots and so on. Likewise a nerve cell possesses selective ion channels for the various different ions, so there are sodium channels and potassium channels etc which all have specific parts to play in the electrical behaviour of nerve cells. This rapid movement of electrically charged particles allows brain cells to produce large but brief electrical signals so they can send messages on a millisecond time scale. For example; the basic unit of electrical signalling in the brain cell is a spike of activity lasting about 1 thousandth of a second called an action potential. Action potentials are caused by the sequential opening and closing of sodium channels and potassium channels. Nerve cells can produce a complex and diverse range of electrical signals. This ability stems from the opening and closing of the dozens of varieties of ion channels that have, so far, been discovered.

...and how are they controlled?

Two basic methods have evolved for opening ion channels. The first involves sensitivity to the powerful electrical field across the cell membrane. Changes in this electric field can alter the shape of some ion channels, causing a central channel to open - these are the voltage-dependent channels. The second system of control requires the attachment of a specific chemical signal to a receptor or recognition site on an ion channel; this transmits a change in shape to the central channel. This is the way that neurotransmitters work; these small molecules are secreted by nerve cells and transmit the signal in those places where the electrical signal won't work, such as the synapse.

What happens at a synapse?

Nerve cells make thousands of special connection points with each other called synapses. On one side is a store of neurotransmitter - the chemical signal. On the other side are the specialized ion channels that contain a recognition site for the neurotransmitter. The electrical signal is unable to cross the gap between the two sides of the synapse. When an action potential arrives at the synapse, the voltage change causes calcium channels to open and calcium pours into the cell. This rise in calcium is a trigger for release of neurotransmitters into the synaptic space where they open clusters of ion channels on the other side of the synapse. Different transmitters are used for increasing (glutamate, acetylcholine) or reducing (glycine, gamma-amino-butyric acid) the electrical activity of the recipient cell. The balance between excitatory and inhibitory activity from all synapses will determine the opening of voltage dependent ion channels and another round of electrical activity in the next cell.

Nature's poisonous bounty

Black-spotted puffer fish, Arothron nigropunctatus

Fish: tetrodotoxin - possibly the most renowned animal toxin; named after the four-toothed puffer fish family Tetraodontidae. Famous also as the occasionally deadly raw fish delicacy fugu in Japan. Also found in the blue ringed octopus. Acts on sodium channels.

Plankton: saxitoxin - from the plankton which generate the marine "red tide". Causes paralytic shellfish poisoning of humans - after the shellfish consume the plankton. Acts on sodium channels. Considered sufficiently dangerous to be listed under the Chemical Weapons Convention.

Yellow-banded poison dart frog, Dendrobates leucomelas

Frogs: batrachotoxin - from Phyllobates terribilis, the name says it all, one of the range of poison arrow frogs. Acts on sodium channels.

Snails: conotoxins - a range of poisons from the venom of sea snails which use them to paralyse their prey (fish). Different forms of conotoxins act on sodium and calcium channels.

Snakes: from the krait family, alpha-bungarotoxin - prevents neurotransmitter from acting on acetylcholine receptors on muscle; result paralysis. From the mamba family, dendrotoxin blocks potassium channels. Many snake venoms also contain other chemicals that disable prey by clotting the blood and digesting flesh as well as nerve cell poisons.

The Sydney funnel web spider (Atrax robustus)

Spiders: agatoxins - which block calcium channels and atracotoxins which cause uncontrollable opening of sodium channels are components of the venom injected through the fearsome fangs of the funnel web spider family.

Scorpions: venom components have been found which block potassuim channels and modify sodium channel function.



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