action potentials

action potentials govern our lives. These are the electrical signals that are transmitted along our nerve and muscle fibres. They are essential for the communication of information to, from, and within the brain. Your ability to read this page and to understand its message, to laugh and cry, to think and feel, to see and hear, and to move your muscles, depends on action potentials.

Each action potential (also called an impulse or ‘spike’) is a transient change in the voltage (electrical potential) across the cell membrane. In nerve fibres, action potentials are brief (lasting less than 1 millisecond) and are said to be ‘all-or-nothing’, because they always have pretty much the same amplitude (voltage change), regardless of the intensity of the stimulus that sets them off. Without the capacity to produce these voltage pulses, a nerve could not transmit information over more than a very short distance, because they are such poor electrical conductors that a voltage change at one point rapidly decays as it spreads away from that point. Action potentials are, therefore, essential for signals to be sent over long distances without loss. The use of all-or-nothing pulses means that information has to be coded in digital form (in terms of the frequency of the impulses) rather than in analogue form (variation in amplitude). The frequency of nerve impulses varies with the signal strength — for example, with the intensity of sound in the case of the auditory nerves, or with the amount of pressure on the skin for cutaneous nerve fibres. The stronger the stimulus, the greater the number of action potentials per second, up to a normal maximum of a few hundred per second. A similar strategy (frequency coding rather than amplitude coding) is used by engineers to send light signals along fibre optic cables.

All cells, including nerve and muscle cells, have an electrical gradient across their cell membranes, with the inside of the cell being negative with respect to the outside at rest. This is known as the resting potential, and it is due to the unequal distribution of salts in the intracellular and extracellular fluids. Potassium ions are more concentrated inside the cell, while sodium ions are higher in concentration outside. Left to themselves, these ion concentrations would tend to equalize out: if the cell membrane were to be punctured, potassium would diffuse out of the cell, while sodium would move in, until eventually their intracellular and extracellular concentrations would equilibrate. This does not happen, however, because the cell membrane itself is impermeable to ions like sodium and potassium. Instead, the movement of ions across the membrane is restricted to tiny pores, known as ion channels, whose opening and closing is tightly controlled. At rest, the sodium channels are closed, but some potassium channels are open. Potassium ions therefore tend to move out of the cell down their concentration gradient, and because they are positively charged, this makes the inside of the cell around 70–80 mV more negative than the outside. The whole system is then roughly in balance, because the negativity inside tends to resist further efflux of potassium ions. There is, however, a very slight leakage of sodium ions into the cell. Over the long run, this is opposed by so-called sodium pumps — protein molecules in the membrane that use energy to push sodium ions out of the cell, in exchange for potassium ions moving in. This quite complex equilibrium is, then, the origin of the resting potential.

By the beginning of the twentieth century, physiologists had discovered that the action potential involves a temporary reversal of the electrical gradient across the nerve cell membrane — the inside of the cell rapidly becomes positive (depolarization) and then equally rapidly reverts to its negative resting state (repolarization). Studies of the giant axon of the squid (the motor nerve that connects to the muscles of propulsion), by Alan Hodgkin and Andrew Huxley in the Marine Biological Laboratories at Plymouth, England, in the 1940s, showed that this is due to time-dependent changes in the permeability of the cell membrane to sodium and potassium ions. World War II broke out before they could write up their results and it was not until 1952 that they published a series of seminal papers that were to win them the Nobel Prize in 1963. Subsequently, a new technique (patch clamping), invented by the German physiologists Erwin Neher and Bert Sakmann (also Nobel Prize winners, in 1991), provided insight into the molecular actions of the ion channels that underlie the action potential.

Action potentials can be triggered by any local depolarization of a nerve that exceeds a certain threshold (usually about 10 mV but sometimes up to 50 mV). In the laboratory, brief electrical stimulation can be employed to set off an action potential at any point in a nerve or muscle fibre. However, in normal circumstances, impulses are usually initiated only in sense organs and in the axon hillock — the point at which the nerve axon emerges from the cell body of a neuron. In sensory receptors, physical or chemical stimulation triggers changes in the membrane that result in local depolarization. In the cell body, depolarization occurs when an excitatory neurotransmitter is released by the terminals of nerve fibres ending in synapses on the cell. The local depolarization directly influences specialized ion channels, producing an initial opening of ‘voltage-gated’ sodium channels, followed shortly afterwards by opening of voltage-gated potassium channels. Because the sodium channels open more quickly than the potassium channels there is an initial inward flow of sodium ions. The positive charge that they carry produces a further membrane depolarization, which activates additional sodium channels, so depolarizing the membrane even further. This explosive reaction causes the rapid initial phase of the impulse, reversing the internal potential.

The amplitude of the action potential (which is typically more than a tenth of a volt) is limited by two processes. First, the sodium channels enter a specialized closed state known as the inactivated state, which curtails the depolarizing flow of sodium ions. Secondly, voltage-gated potassium channels open and the resulting outward potassium current returns the membrane potential to its resting level. The changes in potential that make up an action potential involve the movement of very small numbers of sodium and potassium ions, but, in the long run, the ion concentration gradients would degrade unless restored by the sodium–potassium pump.

Other kinds of ions, flowing through their own specialized channels, may contribute to the action potentials of nerve and muscle fibres. For example, calcium entry plays a part in the action potentials of heart muscle, and chloride flow is important in the electrical activity of skeletal muscle. As might be expected, mutations in the genes that encode ion channel proteins produce a range of nerve and muscle diseases in man. These include epilepsy, cardiac conduction abnormalities, and the muscle disorders known as myotonias.

Nerve axons come in two varieties: myelinated and unmyelinated. Myelin is a fatty sheath that surrounds the myelinated fibres and allows faster transmission of nerve impulses. Action potentials race along myelinated nerve fibres at rates of up to 100 metres/second or more, but can barely manage 1 metre/second in many unmyelinated fibres. The rate at which action potentials are transmitted also depends on temperature, and conduction slows down when the nerve is cooled. This explains why your fingers have difficulty in buttoning your jacket on a frosty morning and why ‘cold-blooded’ animals like insects and lizards, which do not maintain a constant body temperature, move around more slowly in the cold.

Frances Ashcroft

Bibliography

Hodgkin, A. L. (1963). The conduction of the nervous impulse. Liverpool University Press.

See also sensory receptors; refractory period; synapse.