All animal cell membranes contain a protein pump called the Na⁺K⁺ATPase. This uses the energy from ATP splitting to simultaneously pump 3 sodium ions out of the cell and 2 potassium ions in. If this was to continue unchecked there would be no sodium or potassium ions left to pump, but there are also sodium and potassium ion channels in the membrane. These channels are normally closed, but even when closed, they "leak", allowing sodium ions to leak in and potassium ions to leak out, down their respective concentration gradients.

The combination of the Na⁺K⁺ATPase pump and the leak channels cause a stable imbalance of Na⁺ and K⁺ ions across the membrane. This imbalance causes a potential difference across all animal cell membranes, called the membrane potential. The membrane potential is always negative inside the cell, and varies in size from –20 to –200 mV in different cells and species. The Na⁺K⁺ATPase is thought to have evolved as an osmoregulator to keep the internal water potential high and so stop water entering animal cells and bursting them. Plant cells don’t need this as they have strong cells walls to prevent bursting.

In nerve and muscle cells the membranes are electrically excitable, which means that they can change their membrane potential, and this is the basis of the nerve impulse. The sodium and potassium channels in these cells are voltage-gated, which means that they can open and close depending on the voltage across the membrane.

The nature of the nerve impulse was discovered by Hodgkin, Huxley and Katz in Plymouth in the 1940s, for which work they received a Nobel prize in 1963. They used squid giant neurones, whose axons are almost 1mm in diameter, big enough to insert wire electrodes so that they could measure the potential difference across the cell membrane. In a typical experiment they would apply an electrical pulse at one end of an axon and measure the voltage changes at the other end, using an oscilloscope:

The normal membrane potential of these nerve cells is –70mV (inside the axon), and since this potential can change in nerve cells it is called the resting potential. When a stimulating pulse was applied a brief reversal of the membrane potential, lasting about a millisecond, was recorded. This brief reversal is called the action potential:

The action potential has 2 phases called depolarisation and repolarisation.

Depolarisation. The stimulating electrodes cause the membrane potential to change a little. The voltage-gated ion channels can detect this change, and when the potential reaches –30mV the sodium channels open for 0.5ms. The causes sodium ions to rush in, making the inside of the cell more positive. This phase is referred to as a depolarisation since the normal voltage polarity (negative inside) is reversed (becomes positive inside).

Repolarisation. When the membrane potential reaches 0V, the potassium channels open for 0.5ms, causing potassium ions to rush out, making the inside more negative again. Since this restores the original polarity, it is called repolarisation.

The Na⁺K⁺ATPase pump runs continuously, restoring the resting concentrations of sodium and potassium ions.

In the squid experiments the action potential was initiated by the stimulating electrodes. In living cells they are started by receptor cells. These all contain special sodium channels that are not voltage-gated, but instead are gated by the appropriate stimulus (directly or indirectly). For example chemical-gated sodium channels in tongue taste receptor cells open when a certain chemical in food binds to them; mechanically-gated ion channels in the hair cells of the inner ear open when they are distorted by sound vibrations; and so on. In each case the correct stimulus causes the sodium channel to open; which causes sodium ions to flow into the cell; which causes a depolarisation of the membrane potential, which affects the voltage-gated sodium channels nearby and starts an action potential.

Once an action potential has started it is moved (propagated) along an axon automatically. The local reversal of the membrane potential is detected by the surrounding voltage-gated ion channels, which open when the potential changes enough.

The ion channels have two other features that help the nerve impulse work effectively:

• After an ion channel has opened, it needs a "rest period" before it can open again. This is called the refractory period, and lasts about 2 ms. This means that, although the action potential affects all other ion channels nearby, the upstream ion channels cannot open again since they are in their refractory period, so only the downstream channels open, causing the action potential to move one-way along the axon.
• The ion channels are either open or closed; there is no half-way position. This means that the action potential always reaches +40mV as it moves along an axon, and it is never attenuated (reduced) by long axons. In other word the action potential is all-or-nothing.

Action potentials can travel along axons at speeds of 0.1-100 m/s. This means that nerve impulses can get from one part of a body to another in a few milliseconds, which allows for fast responses to stimuli. (Impulses are much slower than electrical currents in wires, which travel at close to the speed of light, 3x10⁸ m/s.) The speed is affected by 3 factors:

• Temperature. The higher the temperature, the faster the speed. So homoeothermic (warm-blooded) animals have faster responses than poikilothermic (cold-blooded) ones.
• Axon diameter. The larger the diameter, the faster the speed. So marine invertebrates, who live at temperatures close to 0°C, have developed thick axons to speed up their responses. This explains why squid have their giant axons.
• Myelin sheath. Only vertebrates have a myelin sheath surrounding their neurons. The voltage-gated ion channels are found only at the nodes of Ranvier, and between the nodes the myelin sheath acts as a good electrical insulator. The action potential can therefore jump large distances from node to node (1mm), a process that is called salutatory propagation. This increases the speed of propagation dramatically, so while nerve impulses in unmyelinated neurons have a maximum speed of around 1 m/s, in myelinated neurons they travel at 100 m/s.

synapse

The junction between two neurons is called a synapse. An action potential cannot cross the synaptic cleft between neurons, and instead the nerve impulse is carried by chemicals called neurotransmitters. These chemicals are made by the cell that is sending the impulse (the pre-synaptic neuron) and stored in synaptic vesicles at the end of the axon. The cell that is receiving the nerve impulse (the post-synaptic neuron) has chemical-gated ion channels in its membrane, called neuroreceptors. These have specific binding sites for the neurotransmitters

The human nervous system uses a number of different neurotransmitter and neuroreceptors, and they don’t all work in the same way. We can group synapses into 5 types:

One neuron can have thousands of synapses on its body and dendrons. So it has many inputs, but only one output. The output through the axon is called the Grand Postsynaptic Potential (GPP) and is the sum of all the excitatory and inhibitory potentials from all that cell’s synapses. If there are more excitatory potentials than inhibitory ones then there will be a GPP, and the neuron will "fire", but if there are more inhibitory potentials than excitatory ones then there will not be a GPP and the neuron will not fire.

This summation is the basis of the processing power in the nervous system. Neurons (especially interneuron's) are a bit like logic gates in a computer, where the output depends on the state of one or more inputs. By connecting enough logic gates together you can make a computer, and by connecting enough neurons together to can make a nervous system, including a human brain.