Long distance (10-100 cm) communication presents a major problem for organisms based on chemical interactions of substances. Simple diffusion becomes ineffective, even on much smaller scales.
Movement of vesicles along the cytoskeleton achieves rates of 1-2 µm / s, which is reasonable on the cellular scale, but not for whole organisms. (It would take 10 10 seconds or 30 years for a signal carried by vesicle transport to go from the tail end of a brontosaurus to its brain. That's a bit slow to react to an attacking T. rex.) Hormone signals can be distributed rapidly in blood, but act as a whole-body broadcast and are not easily targetted to specific destinations.
Electrical transmission of nerve impulses achieves the speed needed, while allowing multiple signals to travel side by side to different destinations in the brain or body. Nerve cells make use of membrane potential generated by the pumping action of Na + /K + ATPase. While membrane potential is found in most cells of the body, the nervous system uses it for long-distance signalling by through perturbations in ion flow due to the action of ion selective channels.
If a chamber is separated into two compartments by a membrane that is permeable because of the presence of protein channels, and different concentrations of solute are present on each side, solute will tend to diffuse from high to low concentration.
If the solute is neutral, obviously there is no membrane potential. This is also true if the solute is ionic, and both positive and negative ions are translocated at the same rate, because charge balance is maintained on each side.
If the membrane is selectively permeable to the positive ions but not the negative, the following happens:
Negative ions stay where they are, because they are not allowed across.
The positive ions initially pass across the membrane due to the concentration difference ,
As positive ions become separated from their negative partners, a potential difference builds up between the two compartments such that the voltage opposes further movement of ions . Only 1 cation in 10 6 is sufficient separation to allow the potential to develop.
Note that it is not the left side with 100 mM Na + that becomes positive, but the right side with 1 mM, because there are actually slightly more Na + ions than Cl – ions on the right. The potential that develops opposes movement of more Na + , hence is positive away from the high concentration.

Equilibrium potential is the voltage that exactly balances the concentration difference.
If [Na + ] is high outside , the equilibrium potential will be positive inside .
For sodium gradient at equilibrium, overall
∆
G = 0 where
∆
G = work done by electrical potential + Free energy change to move from [out] to [in]
0 = z F
∆ψ
+ RT ln
[Na
[
Na
+
+ ]
] in out
∆ψ
= –
RT zF ln
[
Na
[
Na
+ ]
+ ] in out
∆ψ
=
RT zF ln
[
Na
[
Na
+
+
]
] out in
When the actual membrane potential is equal to the equilibrium potential, rate of movement of ions is equal in both directions (equilibium state), so there is no net movement.
When several ions are present simultaneously, the relative conductivity of the membrane for each ion determines the contribution that each ion makes. This gives the Goldman equation:
∆ψ
=
RT
F ln
S
P c
[
C
] out
+ S
P a
[
A
] in
S
P c
[
C
] in
+ S
P a
[
A] out where P c
and P a
are permeabilitity coefficients for each cation and each anion species respectively, and [C] and [A] are the respective concentrations of each cation or anion species.
For the nerve cell, the membrane potential is a good approximation to the combined effect of Na + , K + and Cl – . In the resting state, the K + permeability is much greater than Na + or Cl – , and is the dominant contribution to the resting membrane potential of –60 mV (inwards).
inside
K + 139 mM
Na + 12 mM
Cl – 4 mM outside
4 mM
145 mM
116 mM permeability coefficient
5 × 10 –7 cm s –1
5 × 10 –9 cm s –1
1 × 10 –8 cm s –1 potential as sole species
–91 mV
+64 mV
–86 mV
The last column indicates the potential expected for each ionic species on its own. Membrane potential can be made to change without requiring significant change in ion concentrations simply by increasing the permeability coefficient of any one species . This can happen if a particular ion selective channel, e.g. for Na + , is signalled to open by some means.

A signal is received by a nerve cell in the form of neurotransmitters such as acetylcholine. The The upstream nerve cell activates fusion of synaptic vesicles that contain stored acetylcholine with the plasma membrane, and acetylcholine is released into the synaptic cleft. Acetylcholine diffuses across the narrow gap separating cells, and binds to and opens Na + /Ca 2+ -selective ligand gated channels in the receiving cell (Lehninger p.443).
The sudden increase in Na + permeability causes potential to depolarize or rise from –60 mV to about –40 mV.
Voltage gated
Na + channels in the adjacent plasma membrane now open, boosting the potential to about + 30 mV (action potential). In less than
1 ms, the Na + channels are inactivated, and K + channels start to open. This repolarizes the membrane restoring the original negative potential, with a slight overshoot to –75 mV. K + channels are now inactivated, so that this region of the membrane is unable to initiate a new impulse for a short interval (the refractory period).

After about 5 ms, potential returns to the resting potential of –60 mV, and the membrane can trigger another impulse (Lehninger p.444).
Nerve impulses do not vary from the normal +30 mV of the action potential. Instead, intensity of a nerve signal is indicated by the rate at which action potentials are generated, not by the magnitude of the potential. It should also be stressed that the action potential arises by membrane conductivity changes with only minor changes in ion concentration. Only about one K + ion in 10 4 exits the cytoplasm during a single impulse (detected by radioactive tracer measurements). The ion gradients are maintained by the action of Na + /K + ATPase, but nerve transmission does not place a great burden on the pumping system.
Nerve impulses are conducted along extensions of the neuronal cell called axons. The effect of an action potential in one region of the membrane perturbs the membrane potential in adjacent regions, and this triggers the action potential to travel as a wave down the axon. Ultimately, the action potential reaches the synaptic terminal at the end of the axon, and this triggers neurotransmitter release to pass the signal on to a downstream nerve cell.
Transmission of the axonal wave is speeded up by insulating the axon with a multilayer myelin membrane . Gaps in the myelin occur about every millimeter and are called nodes of Ranvier .

The nerve signal jumps from node to node, and this saltatory conduction speeds up propagation of the signal to about 100 m s –1 instead of < 10 m s –1 . Diameter of unmyelinated axons increases as a function of length, and unmyelinated axons of squid are among the largest single cells known.
The nervous system of animals is a target for a variety of very potent toxins:
Digitoxin (foxgloves) and ouabain (arrow poison from an African tree) inhibit the Na + /K + ATPase.
This causes increase in intracellular Na + , and a consequent increase in cardiac intracellular Ca 2+ .
Moderate doses of digitoxin increase the strength of the Ca 2+ signal that signals muscle contraction, and this makes the heart beat more strongly. Needless to say the dosage has to be controlled very carefully.
Tetrodotoxin (puffer fish or fugu , a Japanese delicacy), scorpion venom and saxitoxin (red tide contamination of shellfish) act by blocking the Na + voltage gated channels.
Batrachotoxin (South American arrow poison frog) binds to Na + channels and leaves them open so that the neuron membrane is permanently depolarized..