Control and coordination

Two coordinating systems: nervous and endocrine

Every activity of a multicellular organism has to be coordinated with the others, some of it within milliseconds and some of it more slowly, and mammals use two systems to do it. The nervous system carries electrical impulses along neurones, which run in fixed pathways from receptors to effectors, so its responses are fast, precisely targeted and short-lived. The endocrine system uses hormones: chemicals secreted by endocrine glands straight into the blood, because endocrine glands are ductless and have no duct to carry their secretion away, and carried in the plasma to cells anywhere in the body. A hormone reaches every cell, but it changes the behaviour of only its target cells, because only those cells carry the complementary receptor protein on the cell surface membrane or inside the cell.

Three named hormones show how wide the range of the endocrine system is. ADH (antidiuretic hormone) is made by neurosecretory cells in the hypothalamus and released from the posterior pituitary gland; it travels in the blood to the walls of the collecting ducts of the kidney, where it makes them more permeable to water so that more water is reabsorbed, producing a smaller volume of more concentrated urine. Glucagon is secreted by the alpha cells of the islets of Langerhans in the pancreas when the blood glucose concentration falls; it targets liver cells and stimulates the breakdown of glycogen to glucose and the conversion of amino acids to glucose, so blood glucose rises. Insulin is secreted by the beta cells of the same islets when blood glucose rises; it targets liver, muscle and adipose cells and stimulates them to take up glucose and to store it as glycogen and fat, so blood glucose falls.

The two coordinating systems are not rivals, and they are not separate: the hypothalamus links them, because it contains neurosecretory cells that release hormones such as ADH and also controls the anterior pituitary gland, which directs the thyroid, adrenal cortex and gonads. This is why the same stimulus, such as a fall in blood water potential or the sight of food, can produce both a nervous and an endocrine response.

Neurones: sensory, intermediate and motor

A neurone is a cell specialised for conducting impulses. It has a cell body containing the nucleus, cytoplasm, mitochondria and rough endoplasmic reticulum, and one or more long thin processes. The cell surface membrane carries the ion channels and the sodium-potassium pumps that make an impulse possible, and the process that carries the impulse away from the cell body is the axon. In most vertebrate neurones the axon is wrapped in a myelin sheath laid down by Schwann cells.

A sensory neurone carries impulses from a receptor to the central nervous system. Its cell body lies outside the central nervous system, in a swelling called a ganglion on a dorsal root of the spinal cord, and only one process leaves the cell body: a long dendron that branches into many dendrites at the receptor end, plus an axon that runs into the spinal cord. The many dendrites increase the surface area available for receiving information from the receptor. The function follows the structure: impulses enter at the dendrites near the receptor and travel along the dendron, through the cell body and along the axon into the central nervous system.

A motor neurone carries impulses from the central nervous system to an effector, which is a muscle or a gland. Its cell body lies inside the central nervous system, in the grey matter of the spinal cord or the brain, with many short dendrites branching from it to collect impulses from other neurones, and one long axon leaves the spinal cord and ends in motor end plates on the muscle fibres or in the gland. Both types of neurone have the same basic components, but the position of the cell body and the lengths of the processes are reversed, and that is the difference most often asked for in an exam.

Intermediate neurones, also called relay neurones, lie entirely within the central nervous system. They have many short processes, no long axon, and they connect sensory neurones to motor neurones, forming the second synapse of a reflex arc. They do more than just pass the message on: because one sensory neurone synapses with several intermediate neurones, one stimulus can produce several responses at once, such as pulling away and turning the head, and intermediate neurones also receive impulses from the brain so that a reflex can be modified or suppressed.

• Sensory neurone: cell body in a ganglion outside the central nervous system, a long dendron that branches into dendrites near the receptor, and an axon that runs into the central nervous system; it conducts impulses from a receptor to the central nervous system.
• Motor neurone: cell body in the grey matter of the central nervous system, many short dendrites on the cell body and one long axon that ends at a motor end plate; it conducts impulses from the central nervous system to an effector.
• Intermediate (relay) neurone: found only inside the central nervous system, with many short processes; it connects a sensory neurone to a motor neurone.
• All three have a cell surface membrane with ion channels and sodium-potassium pumps, and a cell body with mitochondria and rough endoplasmic reticulum to make proteins such as the ion channels.

Sensory receptor cells: from stimulus to impulse

A sensory receptor cell is a transducer: it converts the energy of a stimulus, such as light, pressure, a dissolved chemical or heat, into the electrical energy of a membrane potential. The stimulus alters the permeability of part of the receptor cell membrane, so ions move across it and the potential difference across the membrane changes. This graded change is the generator potential (receptor potential), and its size is proportional to the strength of the stimulus. Each receptor is specialised for one kind of stimulus: chemoreceptors respond to dissolved chemicals, mechanoreceptors such as the Pacinian corpuscle in the skin respond to pressure, which deforms the membrane and opens stretch-mediated sodium channels, photoreceptors respond to light, and thermoreceptors to temperature.

A taste bud in the epithelium of the tongue is a group of chemoreceptor cells. Each cell has fine microvilli projecting into a small opening, the taste pore, where substances from food have been dissolved in saliva. When a dissolved substance binds to a receptor protein in the microvilli membrane, ion channels in the cell surface membrane open and ions diffuse into the cell, so the receptor cell is depolarised and a generator potential builds up. The size of that potential depends on how much of the substance is bound, which is why a stronger taste produces a bigger generator potential.

If the generator potential reaches the threshold value, the sequence continues. Voltage-gated calcium channels in the membrane of the chemoreceptor cell open, calcium ions enter and cause neurotransmitter to be released from the cell across a synapse onto the dendrites of a sensory neurone. The neurotransmitter depolarises the sensory neurone; if that depolarisation also reaches its threshold, an action potential is set up and travels along the axon towards the brain. From the tongue, impulses travel along the facial, glossopharyngeal and vagus nerves to the medulla, and then to the thalamus and the cerebral cortex, which is where the taste is actually perceived.

The strength of the stimulus is coded by the frequency of the impulses, not by their size. All action potentials in a given neurone are the same size, so a stronger stimulus cannot produce a bigger impulse; instead it produces a larger generator potential, more neurotransmitter is released, and the sensory neurone fires more impulses per second. A stimulus that is too weak to reach the threshold produces no impulses at all, which is why a very faint taste is simply not detected.

Resting potential, action potential and the refractory period

A neurone that is not being stimulated has a resting potential of about -70 mV, with the inside of the axon negative relative to the outside, and this is maintained in three ways. First, the sodium-potassium pump in the axon membrane actively transports three sodium ions out of the axon for every two potassium ions it moves in, using ATP, which makes the inside more negative and builds up concentration gradients with much more potassium inside the axon and much more sodium outside. Second, the membrane is far more permeable to potassium than to sodium, because most of the ion channels that are open in a resting membrane are potassium channels, so potassium ions leak out down their concentration gradient, while almost all of the voltage-gated sodium channels are closed. Third, the cytoplasm contains relatively impermeable negatively charged proteins that are too large to leave the axon.

A stimulus at or above the threshold opens some voltage-gated sodium channels, and sodium ions diffuse in down their electrochemical gradient. The entry of positive charge makes the inside less negative (depolarisation), and as the potential rises, more voltage-gated sodium channels open, so more sodium ions enter and the change accelerates in a positive feedback loop. When the membrane potential reaches about +40 mV, the sodium channels close and become inactivated and voltage-gated potassium channels open, so potassium ions diffuse out and the potential falls back (repolarisation). The potassium channels are slow to close, so slightly too much potassium leaves and the potential dips a little below the resting value; the sodium-potassium pump then restores the original ion distribution and the resting potential.

The refractory period follows every action potential. During the absolute refractory period the voltage-gated sodium channels are inactivated and cannot be made to open, so no new action potential can be produced, however strong the stimulus. In the relative refractory period that follows, the potassium channels are still open and the membrane is hyperpolarised, so only a stimulus larger than usual can start a further action potential. When the pump has restored the gradients, the neurone is fully recovered and can be stimulated normally again.

The refractory period has two important consequences. Because the region of axon just behind an impulse is still refractory, it cannot be re-excited, so the impulse can only travel forwards: the refractory period is what makes transmission along a neurone one way. It also puts a ceiling on the information a neurone can carry, because a new impulse cannot be generated until the previous one has ended, so the maximum frequency of impulses is set by the length of the refractory period.

Myelinated neurones and saltatory conduction

In a myelinated neurone the axon is wrapped by a series of Schwann cells, which grow around it and lay down the myelin sheath, a membrane rich in lipid. Myelin is a good electrical insulator, so ions cannot cross the axon membrane wherever it is covered, and the only places where the membrane is exposed are the small gaps between successive Schwann cells, the nodes of Ranvier. The axoplasm is also a good conductor, so the current set up by the movement of ions at one node can flow along the inside of the axon to the next.

Depolarisation can therefore happen only at the nodes, and that changes the way the impulse travels. When the membrane at one node depolarises, the local circuit of current flows through the myelinated stretch of axon to the next node and depolarises the membrane there, so the next action potential is generated at the node and not along the way. The impulse appears to jump from node to node, which is why the process is called saltatory conduction. Because the action potential is generated only at the nodes, far fewer sodium ions have to enter and far fewer potassium ions have to leave, so fewer sodium-potassium pump cycles are needed to restore the gradients and the neurone uses less ATP.

Saltatory conduction makes the impulse travel much faster. An unmyelinated axon conducts at around 1 m/s or less, while a myelinated axon of the same diameter conducts at tens of metres per second, which matters when the effector is a long way from the receptor: in a giraffe, impulses from the foot to the spinal cord have more than a metre to travel. Axon diameter matters as well, because a wider axon has a lower resistance to the flow of current along its inside, so conduction is faster; the giant axon of the squid is fast partly because it is up to a millimetre across, which is far too expensive a solution for a mammal.

Because the myelin sheath is essential, damage to it is serious. In multiple sclerosis the immune system attacks the myelin of neurones in the central nervous system, so the sheaths are destroyed in patches called lesions and the exposed membrane between them can no longer conduct efficiently. Conduction slows, becomes unreliable or fails altogether, and the person has blurred vision, numbness, weakness and loss of coordination, which come and go as myelin is repaired and then attacked again. Demyelination also shows why saltatory conduction is used: replacing the myelinated stretches with more axoplasm would take far more space, and would cost a great deal more ATP.

The cholinergic synapse

A synapse is the junction between two neurones, and at a cholinergic synapse the neurotransmitter is acetylcholine. The presynaptic knob at the end of the axon contains vesicles of acetylcholine, mitochondria that supply ATP, and voltage-gated calcium channels in its membrane. The synaptic cleft between the presynaptic and postsynaptic membranes is about 20 nm wide, and the postsynaptic membrane of the next neurone carries acetylcholine receptor proteins and has acetylcholinesterase associated with it and in the cleft.

When an action potential arrives at the presynaptic knob its membrane is depolarised, and the voltage-gated calcium channels open. Calcium ions diffuse into the knob down their electrochemical gradient, because the calcium concentration outside the neurone is much higher than inside it. The calcium ions cause the vesicles to move to the presynaptic membrane and fuse with it, so the acetylcholine is released into the cleft by exocytosis. The acetylcholine then diffuses across the cleft and binds to the receptor proteins on the postsynaptic membrane. These receptors are chemically gated sodium channels, so they open and sodium ions diffuse in; if enough sodium enters to reach the threshold, a new action potential is set up in the postsynaptic neurone.

The signal has to be switched off as well as switched on. Acetylcholinesterase in the cleft hydrolyses acetylcholine into choline and ethanoic acid, the choline is taken back into the presynaptic knob and re-used to make more transmitter, and the acetylcholine is therefore removed from the receptors. Without this, the postsynaptic membrane would stay depolarised and the neurone would fire continuously.

The synapse gives the nervous system properties that bare neurones could not have. Transmission is one way, because the vesicles of transmitter are only in the presynaptic knob and the receptors are only on the postsynaptic membrane. Many neurones can converge on one neurone, or one neurone can diverge onto many, and impulses arriving at different synapses close together in time can be summed, which is how a neurone decides whether to fire. Because the synapse depends on enzymes, receptors and ion channels, it is also the site where drugs and poisons act. Nerve gases such as sarin and organophosphate insecticides inhibit acetylcholinesterase, so acetylcholine is not broken down, the postsynaptic membrane stays depolarised, impulses fire continuously and the muscles go into spasm; local anaesthetics such as procaine instead block the voltage-gated sodium channels in the membrane, so no depolarisation and no impulse can occur.

From the neuromuscular junction to the sliding filaments

The junction between a motor neurone and a muscle fibre is a neuromuscular junction, where the axon ends in a motor end plate against the sarcolemma, the cell surface membrane of the muscle fibre. It works in the same way as a cholinergic synapse: the arriving action potential opens calcium channels in the presynaptic membrane, acetylcholine is released by exocytosis and diffuses across the cleft, and it binds to receptors on the sarcolemma, which is depolarised. The difference is the size of the response, because enough transmitter is released to depolarise the sarcolemma well beyond the threshold, so every impulse that reaches the junction sets off a contraction of that fibre.

The depolarisation does not stop at the surface of the fibre. The sarcolemma is continuous with the T-tubule system, a set of narrow inward folds of the membrane that run deep into the fibre and pass between the myofibrils. The T-tubules carry the depolarisation quickly to the centre of the fibre, and they lie very close to the sarcoplasmic reticulum, which is a modified endoplasmic reticulum that stores calcium ions. The wave of depolarisation in the T-tubules opens calcium channels in the membrane of the sarcoplasmic reticulum, so calcium ions are released into the sarcoplasm and the contraction begins.

Electron micrographs show that a muscle fibre is packed with myofibrils, and each myofibril is made of repeating units called sarcomeres. A sarcomere runs from one Z line to the next. Within it, the wide dark A band is the region containing the thick filaments of the protein myosin, and the lighter H zone in the middle of the A band is the part of the myosin that has no actin over it. The narrow light I band contains only the thin filaments of actin, which are attached to the Z lines at each end of the sarcomere. The regular alternation of A bands and I bands is what makes striated muscle look striped, and because every sarcomere in the fibre contracts at the same time, the whole fibre shortens when each of its sarcomeres becomes shorter.

The sliding filament model explains the shortening. In a relaxed muscle the binding sites for myosin on the actin filaments are blocked by tropomyosin, which is held in position by troponin. When calcium ions are released from the sarcoplasmic reticulum they bind to troponin, which changes shape and pulls the tropomyosin away, exposing the binding sites. The myosin heads, which are already tilted back and carry ADP and an inorganic phosphate, attach to the exposed sites to form cross-bridges, and each head then changes angle in a power stroke, pulling the actin filament a short distance towards the centre of the sarcomere. ATP then binds to the myosin head, which allows the head to detach from the actin; the ATP is hydrolysed by the myosin ATPase and the energy released tilts the head back so that it can attach again further along the actin filament. The cycle is repeated many times, so the actin filaments are pulled inwards and slide over the myosin filaments, the Z lines are drawn closer together, and the I band and the H zone become narrower while the A band keeps exactly the same width. ATP is also needed to pump the calcium ions back into the sarcoplasmic reticulum by active transport, and when the calcium is removed the troponin and tropomyosin return to their positions and the muscle relaxes.

Coordinating plant responses: the Venus fly trap, auxin and gibberellin

Plants have no nerves and no muscles, yet some of them respond to a stimulus within a fraction of a second. The Venus fly trap, Dionaea muscipula, grows in wet, nutrient-poor bogs in North and South Carolina, where the soil contains too few nitrates for normal growth, so it obtains nitrogen by catching insects. Each trap is a modified leaf with two lobes, and each lobe carries three stiff trigger hairs. The trap closes only if a hair is stimulated twice, or two different hairs are stimulated, within about 20 seconds, which prevents it snapping shut on a raindrop or a fallen leaf and wasting both the energy and the several hours it takes to reset. Bending a trigger hair deforms a sensory cell at its base and produces a receptor potential, and if the threshold is reached an action potential is generated and spreads through the leaf tissue; the second stimulus within the short time produces further action potentials that sum with the first and take the tissue past the threshold. The closure itself is a rapid movement of water. The action potential makes ions move across the membranes of the cells in the lobes and the hinge that joins them, so water follows osmotically: cells on one side of the hinge take up water and their turgor rises while the cells on the other side lose water and their turgor falls, and because the two layers change length by different amounts the lobes bend inwards and the trap snaps shut. The insect is then digested by enzymes secreted into the closed trap, which provides the plant with nitrogen.

Auxin is a plant growth regulator that controls elongation growth. The natural auxin is indoleacetic acid (IAA), which is made mainly in the apical meristems of shoot tips and in young leaves, and it moves from cell to cell down the stem. Auxin stimulates cell elongation, but only up to a point: a low concentration promotes growth and a high concentration inhibits it, which is why a concentration that makes a shoot cell elongate has that effect in the shoot but is far too high for a root, where a much lower concentration is needed. In a shoot, auxin produces the bending seen in phototropism. When light comes from one side, auxin is transported away from the illuminated side, so the shaded side has a higher concentration, its cells elongate more, and the shoot bends towards the light. This is why a houseplant left by a window grows towards the glass.

Auxin brings about elongation growth by stimulating proton pumping. When auxin binds to receptors in the cell surface membrane, it activates proton pumps or H+-ATPases, which use ATP to pump hydrogen ions out of the cytoplasm and into the cell wall. The wall becomes more acidic, and the lower pH activates wall-loosening and cell-wall enzymes that break the bonds between the cellulose microfibrils. The wall is now more extensible, so the turgor pressure of the cell pushes it outwards and the cell takes in more water and stretches. Because the wall has been loosened, the stretch is not reversed when the pressure changes, and the cell ends up permanently longer. This is why auxin has to be present when the wall is loosened: without it, the wall is too rigid for the cell to extend.

Gibberellin is a plant growth regulator that promotes stem elongation, fruit development and the germination of seeds, and its role in the germination of barley is well established. When a barley grain takes up water, the embryo becomes active and secretes gibberellin, which diffuses to the aleurone layer, the protein-rich layer just beneath the testa. There the gibberellin stimulates the transcription of genes for the enzyme alpha-amylase, so the aleurone layer synthesises the enzyme and secretes it into the endosperm, which is a store of starch. The alpha-amylase hydrolyses the starch to maltose and other sugars, and these diffuse back to the embryo and are respired to supply the ATP and the carbon that the growing seedling needs until its leaves are above ground and photosynthesis can begin; gibberellin also stimulates the production of proteases, which release amino acids from the storage protein. Take the gibberellin away and the grain cannot mobilise its starch store. The malting industry uses the same mechanism deliberately: barley is steeped in water and allowed to germinate so that alpha-amylase breaks the starch down to sugars, and germination is then stopped by drying the grain in a kiln, leaving the sugars for yeast to ferment in brewing and distilling. Gibberellic acid (GA3) is also sprayed on crops such as sugar cane and grape vines to increase stem length and fruit size.