Nerve cells, nerve impulses

Structure of the neurone

Nerve cells - neurones or neurons - have all the normal features of body cells: a cell membrane enclosing the cytoplasm and a nucleus, but there are some modifications related to their specific function - the passage of nervous impulses. Some neurones can be quite long - the length of a limb. They provide a pathway for the flow of information from one part of the body to another, as well as the processing of that information, possibly preventing information from proceeding.


An unmyelinated motor neurone
[Nerve impulse passes from left to right]
Structures not shown on the diagram above (and functions) :

• mitochondria in cell body and terminal bulbs (aerobic respiration)
• prominent Nissl granules/bodies - endoplasmic reticulum with rosettes of free ribosomes - in cell body only (protein synthesis)
• microtubules along axon (transport of proteins etc from cell body)
• axon also contains 10nm diameter neurofilaments composed of polypeptide chains related to keratin (structural support)

Neurones have thin extensions - also known as nerve fibres - bringing impulses into and away from the cell. Dendrites bring impulses in, and the axon takes impulses away from the cell body.

Some neurones generate impulses as a result of detecting a stimulus. Others pass on impulses to other neurones and then to muscles or glands.
There are many types/shapes of neurone, and it is helpful to consider sensory, relay/intermediate and motor neurones, especially in the context of a reflex action.

The more numerous neuroglial cells perform a support function. Schwann cells and oligodendrocytes (see below) are examples of neuroglial cells.

Types of neurones

Within the peripheral nervous system there are 3 main types of neurone:

• sensory neurones - which collectively make up afferent nerves - inputs to the nervous system, and
• interneurones which pass on impulses from sensory neurones, up the spinal cord to the brain, or directly on to :
• motor neurones - which collectively make up efferent nerves - causing muscles to contract, or innervating glands

[Nerve impulse passes from right to left]
A sensory neurone typically has its cell body off to one side of the main tubular process that carries nerve impulses. The (usually much longer) section carrying impulses from the receptor (sometimes known as a nerve ending) is called the dendron, and the (usually much shorter) section leading away is called the axon.
See below for more information about the myelin sheath and nodes of Ranvier.


[Nerve impulse passes from top to bottom]
Interneurones - also known as relay neurones - are cells that pass on impulses within the central nervous system. They are smaller, as the axon is quite short. They generally do not have myelin sheaths.

More about the axon

In some cases the axon can be quite long. It has a cylindrical membrane consisting of a phospholipid bilayer, with a number of proteins embedded in it. Some of these may function as pumps for the active transport of ions across the membrane, or as ion channels, permitting the passage of specific ions by diffusion. The cytoplasm inside the axon (axoplasm) usually differs chemically from the liquid outside (extracellular fluid).

Some neurones (especially longer ones in the peripheral nervous system of vertebrates) have an outer coating consisting of a number of cells wound around their axons. These cells - Schwann cells - present several layers of membrane, containing a white fatty material called myelin on the outside of the axon membrane.


A myelinated motor neurone
This sort of neurone is much more efficient than an unmyelinated one and it transmits impulses at a greater speed - see below.

Accessory cells called oligodendrocytes perform a similar function in neurones of the central nervous system. In fact within the brain there are distinct areas of so-called grey matter: mostly cell bodies of neurones, and white matter: myelinated neurones.

How a Schwann cell myelinates (part of) an axon

A single neurone can have hundreds of Schwann cells wrapped around its axon. Each Schwann cell is about 0.1 mm in length, so an axon that is 1 m in length would have about 10,000 Schwann cells.
Each Schwann cell spreads out and then grows round the axon, then over itself several times.
The result is rather like a Swiss roll.


These 2 pictures show sections across an unmyelinated (A) and a myelinated nerve (B), each consisting of many axons - seen as purple dots. Interestingly, Schwann cells can assist the body in the event of nerve damage. A broken axon will re-grow from the cell body, and follow the path of the Schwann cells to the original destination. This regeneration is very slow - 1 to 5 mm per day. Unmyelinated axons do not have the guidance, and rarely succeed in re-growth.

The nature of nervous impulses along the axon

Nervous impulses are different from electrical signals carried along wires, such as from a microphone or to a loudspeaker. Nervous impulses are electrochemical in nature, and the electrical potential (voltage) concerned is generally quite low - generally (tens of) millivolts. They can be measured using sensitive electrical apparatus, and can be generated using electrical stimulation, but they move at a different (much slower) speed. Nervous impulses are also packages of information - similar to digital data as used by computers - rather than changing waveforms in analogue systems. And the fact they are generated within a water-based environment means that a different mechanism is involved.

An impulse can be made to pass along an axon as a result of stimulation by using electrodes attached to a (low voltage) electrical supply. However it has been found that an impulse is not produced if the voltage is too low. An impulse does result if stimulation is above a certain point; a threshold value, but stimulation above this value does not cause a stronger or greater impulse. This is called the all-or-nothing principle.

An apparently inactive neurone has a measurable electrical potential (unlike an unused microphone or speaker). This potential is called the resting potential, and it needs to be established before an impulse can pass. Membrane potentials are measured as the difference between the voltage at a point inside the axon and the fluid outside (generally the same along the whole length of the axon).

In fact at a cellular level the potentials are all caused by the movement of ions, principally potassium (K⁺) and sodium (Na⁺), and specific protein channels in the neurone membrane.

Stimulation of an axon

Electrodes are fine pieces of (platinum?) wire inside small glass tubes filled with a conducting salt solution, inserted through the axon membrane

Click here for interpretation (see above and below): ..1.. ..2.. ..3.. ..4.. ..all.. ..reset..

Resting potential

This is established by the pumping of sodium ions out of, and potassium ions into, the axon, by protein pumps embedded in the membrane. Each sodium/potassium ion pump in fact pumps 3 sodium ions out, and 2 potassium ions in, using one molecule of ATP to do so.
This is active transport, and it depends on aerobic respiration.

The resulting electrochemical gradient - imbalance between sodium ion and potassium ion concentration on either side of the axon membrane - results in a resting potential - generally close to -70 mV. The membrane is said to be polarised.

Although sodium ions and potassium ions are both positively charged (cations), they do not 'cancel each other out' by being on opposite sides of the membrane. In fact they generate a potential difference (voltage) rather similar to a cell in an electrical battery. Other - negatively charged - ions (anions) are also present, primarily as partners to the cations sodium and potassium. Inside the axon there are large anions and negatively charged proteins which do not move, whereas outside the axon there are more chloride ions (Cl^-) which would need specific carrier channels to cross the phospholipid bilayer.

Other details: The axon membrane is slightly leaky (in fact more permeable to potassium ions than to sodium ions) and potassium ions diffuse out faster than sodium ions diffuse in.

In fact the steady outflow of potassium ions (through "leak channels") is responsible for the resting potential. The sodium/potassium ion pump must operate continuously in the background to counteract or balance this.

The sodium/potassium ion pump

This mechanism is found in the membrane of many cell types (not just neurones), where it functions as an osmoregulatory mechanism. Sodium ion gradients power several cellular transport mechanisms.

Action potential

The outer surface of the axon membrane has a positive charge, compared to the inside. When a nervous impulse passes along the axon, voltage-gated sodium ion channels open, causing sodium ions to enter by diffusion, down an electrical/chemical gradient. This causes depolarisation of the membrane at that point, so that here the inside temporarily has a positive charge - typically about +45 mV.

This means that an electrical circuit exists between this (-ve) region and the neighbouring (+ve) section ("adjoining region") of the axon membrane. This sets up a local current, increasing the permeability of the adjoining region as a result of voltage-gated sodium ion channels opening, allowing sodium ions to enter at that point. In fact the voltage change stimulates more sodium ion channels to open - a positive feedback effect. At the peak of the action potential, sodium ion channels close. There is a section within the channel called the inactivation gate which plugs the channel, preventing flow of sodium ions. At a later stage when the resting potential is restored, 'deinactivation' occurs and the neurone can transmit another impulse.

Next, voltage-gated potassium ion channels open and potassium ions diffuse out of the axon, down an electrical/chemical gradient, which works in the opposite direction. This has the effect of reversing the axon surface potential back towards its resting (negative) value: repolarisation.

In fact this reduces the membrane potential below the normal resting potential - hyperpolarisation - shown as "undershoot". The potassium ion channels now (gradually) close. There is a brief period where ions which have recently moved reassort themselves with others on either side of the membrane.

Another action potential cannot pass until the normal resting potential is restored - this gap is called the 'refractory period'. This means that nervous impulses are distinct and discrete pulses, which move in one direction, with distinct gaps (in time) between each.

The depolarisation phase and repolarisation each take about 0.5 ms (1.0 ms total), and the hyperpolarisation phase is often about 3ms, so the maximum frequency is about 250 impulses per second (250 Hz).


Before and after action potential
This process occurs progressively along the length of the axon, so that the action potential gradually moves along it.
This is called the propagation of a nervous impulse, because it involves the repeated creation of an identical event, travelling in a set direction.

It is sometimes said that after an impulse, the sodium/potassium ion pump can once again pump sodium ions out, and potassium ions in. However, the numbers of sodium and potassium ions crossing the membrane at each impulse are insignificant compared with the excess concentrations providing the motive force. It has been shown that (hundreds of) nervous impulses can still be sent after the sodium/potassium ion pump has been inactivated using metabolic inhibitors.

The sodium/potassium ion pump works more or less continuously in the background.

This is the difference it makes

Ion	External concentration	Internal concentration	Equilibrium potential
Na+	460	50	+60mV
K+	20	400	-90mV
Cl-	560	100	-70mV
Organic anions	0	370	?

Ionic concentrations (mmol/dm³) on either side of the (squid) axon membrane
and the equilibrium potentials associated with the differences in ionic concentration

The membrane potential can be calculated from the Goldman-Hodgkin-Katz equation:


where
P_K is the relative membrane permeability for K⁺ ions
[K⁺]_o is the K⁺ ion concentration outside the axon
[K⁺]_i is the K⁺ ion concentration inside the axon
and similarly for Na⁺ and Cl^- ions.

Obviously
R is the universal gas constant (8.314 J.K-1.mol-1)
T is the temperature in Kelvin (K = °C + 273.15)
F is Faraday's constant (96485 C.mol-1)
ln is the log to base e (of the combined fraction)

Since the potassium ion has the highest concentration ratio (inside to outside) and a number of leak channels are open all the time allowing small numbers of potassium ions to leave the axon, it determines the extent of the resting potential - taking it down (about three-quarters of the way) towards the equilibrium potential for potassium. The other ions are negligible at this stage.

During the rising phase of the action potential, permeability to sodium ions rises dramatically as voltage-gated sodium ion channels open, and the membrane potential rises towards the sodium equilibrium potential, reversing the membrane polarity as sodium ions enter the axon.

This is followed by a comparable but extended rise in membrane permeability to potassium ions, again due to voltage-gated ion channels, which allows more potassium ions to move in the opposite direction (out of the axon), taking the membrane potential back down to an even lower value than the resting potential.

Eventually voltage-gated potassium channels close and the membrane is once again dictated by the potassium leak channels.

Chloride ions do not participate in the same way as sodium and potassium ions in nervous impulses along the axon, but they can contribute to inhibitory post-synaptic potentials.

In some neurones and muscle cells, calcium ions contribute to membrane potentials too.

Factors affecting the speed of nervous conduction

Data may be obtained by electrical stimulation of nerve fibres within the body (probably a mixed collection of parallel axons) and monitoring of potential at a distance, or from dissected material. The frog sciatic nerve/gastrocnemius muscle preparation has been used for this purpose. And of course the giant axons of cephalopod molluscs (squid, cuttlefish etc) have proved to be useful as elecrodes are fairly easily inserted into them, and cytoplasm can also be extracted for chemical analysis.

Myelination and Saltatory Conduction

The presence of a myelin sheath increases the speed of conduction of nerve impulses. Myelinated axons conduct impulses about 10 times faster than comparable unmyelinated ones.

The sheath insulates the axon and covers up the section beneath it. An action potential at one end of an axon causes membrane depolarisation, but this does not work its way along under the Schwann cell. Instead it forms a circuit - through the extracellular fluid - with the next section of exposed axon, at the next node of Ranvier. This small area of membrane depolarises, and forms a circuit with the next node of Ranvier, and so on along the axon.

This is called saltatory conduction, because the impulse 'jumps' from node to node along the axon.

Interestingly, myelination is also more efficient in energy terms as the active tranport of ions (Na⁺/K⁺ pumps) only occurs at the nodes of Ranvier, so less ATP is needed and less respiration is required for the restoration of ion balance and membrane repolarisation.

Axon diameter

Axons with larger diameters conduct impulses faster than smaller ones.
This is because of surface area:volume ratio. Leakage of ions is less of an interfering factor in larger axons. It is probably not connected with reduced resistance to liquid flow in larger pipes, as sodium and potassium ions only move laterally across the membrane, not along the axon.

Human axons vary in size, but the majority of them fall into the size range 13-20 µm ; this gives a velocity of 80–120 m/s; others in the range 6-12µm conduct at 33–75 m/s. These are all myelinated.

The giant axons of the Squid range from 0.5-1 mm (500-1000 µm) in diameter, and conduct impulses at a velocity of 25 m/s. However these are not myelinated.
Giant axons transmit impulses to the muscles of the mantle responsible for the swift ejection of water in escape reactions.

Note: this graph is based on fibre diameter (including myelin sheath), not just axon diameter

Temperature

Factors such as speed of diffusion are affected by temperature. Sodium ions diffuse into the axon, and potassium ions diffuse out more quickly, and ion channels open faster. Velocity of nervous impulses increases linearly with temperature, within the normal range (0-40 +? ° C).

Warm-blooded animals have a constant body temperature near to 37 ° C.

On the other hand, the body temperatures of cold-blooded organisms are much more closely allied to their environmental temperature.

Invertebrates living in arctic waters have significantly slower speeds of conduction, and it is thought that they offset this through the use of neurons with higher diameter.

Not the speed of conduction, but ...

The duration of the action potential increases by 3x with each 10 °C rise in temperature .

A video summarising some of the contributions made to neuroscience by this feisty cephalopod

This has become unavailable as an embedded video, but see the YouTube videos in the links below.
The first one starts with a fishing trip, and seems to have a rather authoritative commentary!

Nerve stimulation

The sciatic nerve of a frog has often been dissected out and used in investigations of nervous activity, when stimulated electrically.
The McGill Physiology Virtual Lab Compound Action Potential

Related issues

Multiple sclerosis is an autoimmune disorder of the central nervous system in which the body creates antibodies against myelin in the membrane of the oligodendrocyte, but not to Schwann cells.

Cannabinoids to treat MS

Guillan-Barre disease involves antibodies against Schwann cells but not oligodendrocytes - the peripheral nervous system is affected instead.

Huntington’s disease (HD) causes the death of neurones