3.6.4.2 Control of blood glucose concentration

Okay so to start we should know a little bit about hormones:

• They are all produced in glands which secrete the hormone directly into the blood (endocrine glands)
• carried in the blood plasma to the cells on which they act (target cells). These cells have specific receptors on their cell-surface membranes that are complementary to a specific hormone
• are effective in very low concentrations but often have widespread and long lasting effects

One mechanism of hormone action is the secondary messenger model. This is used by two hormones involved in the regulation of blood glucose concentration (adrenaline and glucagon).

The mechanism involving adrenaline is as follows:

• adrenaline binds to a transmembrane protein receptor within the cell-surface membrane of a liver cell
• this binding causes the protein to change shape on the inside of the membrane
• this protein shape change leads to the activation of an enzyme called adenyl cyclase. The activated adenyl cyclase converts ATP to cyclic AMP (cAMP)
• The cAMP acts as a second messenger that binds to protein kinase enzyme changing its shape and therefore activating it
• the active protein kinase enzyme catalyses the conversion of glycogen to glucose which moves out of the liver cell (by facilitated diffusion) and into the blood.

The pancreas

The pancreas is a gland that is situated in the upper abdomen (behind the stomach). It produces enzymes for digestion (protease, amylase, and lipase) and hormones for regulating blood glucose concentration (insulin and glucagon). Scattered throughout the cells that produce digestive enzymes are groups of hormone-producing cells known as islets of Langerhans. These include:

• alpha cells (which are larger and produce glucagon)
• beta cells (which are smaller and produce insulin)

The liver

This is located below the diaphragm. It is made up of cells called hepatocytes. The hormones that the pancreas produces (glucagon and insulin) have an effect in the liver. There are three processes regarding blood sugar which take place in the liver that we need to learn:

• Glycogenisis
• This is the conversion of glucose to glycogen
• when blood glucose concentration is higher than normal the liver removes glucose from the blood and converts it into glycogen.
• Glycogenolysis
• This is the break down of glycogen to glucose
• when blood glucose concentration is lower than normal the liver can convert stored glycogen to glucose which diffuses into the blood to restore the normal blood glucose concentration
• Gluconeogenesis
• This is the production of glucose from sources other than carbohydrate (e.g glycerol and amino acids) when the supply of glycogen is exhausted.

The beta cells of the islets of Langerhans in the pancreas have receptors that detect a rise in blood glucose concentration. They respond by secreting the hormone insulin directly into the blood plasma. 

Factors that affect blood glucose concentration include:

• diet - in the form of glucose absorbed following hydrolysis of other carbohydrates (e.g starch/maltose/lactose/sucrose)
• glycogenolysis - the break down of glycogen to glucose
• gluconeogenesis - the break down of sources other than carbohydrates into glucose

Insulin

The beta cells of the islets of Langerhans in the pancreas have receptors that detect the stimulus of a rise in blood glucose concentration and respond by secreting insulin. Glycoprotein receptors on cell-surface membranes bind specifically with insulin molecules bringing about:

• a change in the tertiary structure of the glucose transport carrier proteins which causes them to change shape and open allowing more glucose into the cells by facilitated diffusion allowing more glucose in by facilitated diffusion
• an increase in the number of carrier proteins responsible for the transport of glucose
• at low insulin concentrations the protein from which these channels are made is part of the membrane vesicles. A rise in insulin concentration results in these vesicles fusing with the cell-surface membrane so increasing the number of glucose transport channels
• activation of the enzymes that convert glucose to glycogen and fat (glycogenesis)

As a result blood glucose concentration is lowered by:

• increasing the rate of absorption of glucose into the cells
• increasing the respiratory rate of the cells which uses up more glucose thus increasing their uptake of glucose
• increasing the rate of conversion of glucose into glycogen in the liver and muscle cells
• increasing the rate of conversion of glucose to fat

This subsequent lowering of the glucose in the blood causes the beta cells to reduce their secretion of insulin

Glucagon

Alpha cells of the islets of Langerhans detect a fall in blood glucose concentration and respond by secreting the hormone glucagon. Glucagon...

• attaches to specific protein receptors on the cell surface membrane of liver cells
• activating enzymes that convert glycogen to glucose
• activate enzymes involved in the conversion of amino acids and glycerol into glucose

Adrenaline

At times of excitement/stress adrenaline is produced by the adrenal glands above the kidneys. This raises the blood glucose by:

• attaching to protein receptors on the cell-surface membrane of target cells
• activating enzymes that causes the breakdown of glycogen to glucose in the liver

Insulin and glucagon act antagonistically. This means that the concentration of glucose is not constant but fluctuates around an optimum point.

Diabetes

There are two forms of diabetes:

• Type 1
• due to the body being unable to produce insulin
• Control: it is controlled by injections of insulin. 
• Type 2
• due to glycoprotein receptors on body cells being lost/losing their responsiveness to insulin
• Control: regulate the intake of carbohydrate in the diet and match this to an amount of exercise

3.6.4.3 Control of blood water potential

The homeostatic control of water potential of the blood is called osmoregulation. Mammals have 2 kidneys made up of the following:

• a fibrous capsule - an outer membrane that protects the kidney
• a cortex - a lighter coloured outer region made up of Bowman's capsules convoluted tubules. and blood vessels
• medulla - a darker coloured inner region made up of loops of Henle, collecting ducts, and blood vessels
• renal pelvis - a funnel shaped cavity that collects urine into the ureter
• ureter - a tube that carries urine to the bladder
• renal artery - supplies the kidney with blood from the heart via the aorta
• renal vein - returns blood to the heart via the vena cava

The nephron is the functional unit of the kidney. It is a narrow tube with two twisted ends separated by a central hairpin loop. Each one is made up of a:

• Bowman's capsule - cup shaped and surrounds a mass of blood capillaries known as the glomerulus. The inner layer is made up of podocytes
• proximal convoluted tubule - a series of loops surrounded by blood capillaries. Made of thin epithelial cells which have microvilli
• Loop of Henle - a long hairpin loop that extends from the cortex into the medulla of the kidney and back again surrounded by blood capillaries
• distal convoluted tubule - a series of loops surrounded by blood capillaries. Made up of epithelial cells but is surrounded by fewer capillaries than the proximal convoluted tubule
• collecting duct - a tube which a number of distal convoluted tubules empty into. Lined by epithelial cells and widens as it empties into the pelvis of the kidney.

Blood vessels:

• afferent arteriole arises from the renal artery and supplies the nephron with blood
• glomerulus is a many branched knot of capillaries from which fluid is forced out the blood
• efferent arteriole is a tiny vessel that leaves the glomerulus
• blood capillaries is a concentrated network of capillaries that surrounds the proximal convoluted tubule, the loop of Henle, and the distal convoluted tubule from where they reabsorb mineral salts glucose and water. They merge together to form the renal vein.

The nephron works in 4 stages:

• formation of the glomerular filtrate by ultrafiltration
• the walls of the glomerular capillaries are made up of endothelial cells with pores between them. There is a build up of hydrostatic pressure as the diameter of the afferent arteriole is greater than of the efferent arteriole. As a result water/glucose/mineral ions are squeezed out of the capillary to form the glomerular filtrate. Large proteins/blood cells cannot pass across.
• The inner layer of the renal capsule is made up of highly specialised cells canned podocytes. These have gaps between their branches and the filtrate can pass between these cells.
• the endothelium of the glomerular capillaries have spaces up to 100nm wide

• reabsorption of glucose and water by the proximal convoluted tubule
• in the proximal convoluted tubule almost 85% of the filtrate is reabsorbed back into the blood. Due to ultrafiltration most small molecules are removed but most of these are useful so they get reabsorbed
• the proximal convoluted tubules are adapted to reabsorb substances by having epithelial cells that have:
• microvilli
• infoldings to give a large surface area
• a high density of mitochondria to provide ATP for active transport
• The process is as follows:
• sodium ions are actively transported out of the cells lining the proximal convoluted tubule into blood capillaries which carry them away so the sodium concentration of these cells is lowered
• sodium ions diffuse down a concentration gradient from the lumen into the epithelial lining cells by carrier proteins
• these carrier proteins carry another molecule (glucose/amino acids/chloride ions) with them (co-transport)
• the molecule which have been co-transported into the cells of the proximal convoluted tubule diffuse into the blood

• maintenance of a gradient of sodium ions in the medulla by the loop of Henle
• The loop of Henle is responsible for water being reabsorbed from the collecting duct by concentrating the urine so that it has a lower water potential than the blood. The concentration of urine produced is directly related to the length of the loop of Henle. It has two regions: The descending limb (highly permeable to water), and the ascending limb (impermeable to water)
• The loop of Henle acts as a countercurrent multiplier:
• sodium ions are actively transported out of the ascending limb of the loop of Henle using ATP provided by mitochondria in the cells of its wall
• This creates a low water potential/high ion concentration in the region of the medulla between the two limbs (the intestinal region). The thick walls are impermeable to water so very little escapes the ascending limb.
• The walls of the descending limb are permeable to water so it passes out by osmosis into the interstitial space and enters blood capillaries
• the filtrate progressively loses water as it moves down the descending limb lowering its water potential
• at the base sodium ions diffuse out the filtrate and as it moves up the ascending limb these ions are also actively pumped out so the filtrate develops a progressively high water potential
• in the space between the ascending limb and the collecting duct there is a gradient of water potential with the highest in the cortex sand the lowest in the the further down into the medulla
• the collecting duct is permeable to water so as the filtrate moves down it water passes out by osmosis. This passes into blood vessels that occupy this space and is carried away
• As water passes out of the filtrate its water potential is lowered but the water potential is also lowered in the interstitial space so water continues to move out by osmosis down the whole length of the collecting duct. The countercurrent multiplier ensures that there is always a water potential gradient drawing water out of the tubule
• reabsorption of water by the distal convoluted tubule and collecting ducts
• the main role of the distal convoluted tubule is to make final adjustments to the water and salts that are reabsorbed and to control pH of the blood by selecting which ions to reabsorb. The homeostatic control of osmoregulation in the blood is achieved by a hormone that acts on the distal convoluted tubule and the collecting duct.

The body responds to a fall in water potential of the blood as follows:

• osmoreceptors in the hypothalamus (in the brain) detect a fall in water potential and water is lost from the osmoreceptor cells which causes the cell to shrink causing the hypothalamus to produce ADH (antidiuretic hormone)
• ADH passes into the pituitary gland from where it is secreted into the capillaries
• ADH passes into the blood to the kidney
• protein receptors on the cell surface membrane of these cells bind to ADH leading to the activation of an enzyme (phosphorylase). This causes vesicles within the cell to move to and fuse with the cell surface membrane
• These vesicles contain pieces of plasma membrane that have numerous water channel proteins (aquaporins) and the number of water channels is significantly increased when they fuse
• this increases the permeability of the collecting duct to urea which passes out lowering the water potential of the interstitial space
• this causes more water to leave the collecting duct by osmosis and reenter the blood
• this prevents the water potential of the blood from getting any lower

3.6.3 Skeletal muscles are stimulated to contract by nerves and act as effectors

Muscles are effector organs that respond to nervous stimulation by contracting and so bring about movement. They act in antagonistic pairs against an incompressible skeleton. There are three types:

• cardiac muscle (heart)
• smooth muscle (walls on blood vessels and the gut)
• skeletal muscle (attached to bone, under voluntary control)

Individual muscles are made up of tine fibres called myofibrils. They produce very little force but all together are extremely powerful. They are lined parallel to maximise force. Individual muscle cells do not have nuclei etc. The cells have become fused together into muscle fibres which share nuclei and cytoplasm (known as sarcoplasm). Within the sarcoplasm is a large concentration of mitochondria and endoplasmic reticulum.

Myofibrils are made up of two types of protein filament:

• actin
• this is thinner and consists of two strands twisted around eachother
• tropomyosin forms a fibrous strand around the actin filament
• myosin
• this is thicker and consists of long rod-shaped tails with bulbous heads that project to the side

Myofibrils appear striped due to alternating dark and light bands. Light bands are isotropic bands (I-bands) - here the thick (myosin) and thin (actin) filaments do not overlap hence they are lighter in colour. Dark bands are called anisotropic bands (A-bands) - here the myosin and actin filaments overlap hence it appears darker here. At the centre of each A-band is a lighter region known as the H-zone and at the centre of each I-band is a line called the Z-line. The sarcomere is the distance between adjacent Z-lines. When the muscle contracts the sarcomeres shorten.

There are two types of muscle fibre:

• slow-twitch fibres
• contract more slowly and provide less powerful contractions but over a long period
• adapted to endurance work (e.g running a marathon)
• they are suited to this role by being adapted to aerobic respiration to avoid a build up of lactic acid (this would cause them to function less effectively and prevent long-duration contraction)
• they have a large store of myoglobin, a rich supply of blood vessels (to deliver o2 and glucose for aerobic respiration), and numerous mitochondria to produce ATP
• fast-twitch fibres
• contract more rapidly producing more powerful contractions but only for a short period of time
• adapted to intense exercise so are more common in muscles that need to do short bursts of intense activity
• they have thicker and more numerous myosin filaments, a high concentration of glycogen, a high concentration of enzymes involved in anaerobic respiration which provide ATP rapidly, a store of phosphocreatine (a molecule that can rapidly generate ATP from ADP in anaerobic conditions)

A neuromuscular junction is the point where a motor neurone meets a skeletal muscle fibre. It is covered in 3.6.2.2.


The contraction of a skeletal muscle will move a part of the skeleton (e.g a limb) in one direction but the same muscle cannot move it in the other direction as muscles can only pull (not push). A second muscle working antagonistically is required to move the limb in the opposite direction.

The process of contraction involves the actin and myosin filaments sliding past one another so it is known as the sliding filament mechanism. This is supported by the changes seen in band pattern on myofibrils. When a muscle contracts...

• the I-band becomes narrower
• the Z-lines move closer together (the sarcomere shortens)
• the H-zone becomes narrower
• The A-band remains the same width as the width of this band is determined by the length of the myosin filaments and they do not get shorter.

Here's how the mechanism works:

• an action potential reaches many neuromuscular junctions simultaneously causing calcium ion protein channels to open and calcium ions to diffuse into the synaptic know
• the calcium ions cause the synaptic vesicles to fuse with the presynaptic membrane and release their acetylcholine into the synaptic cleft
• acetylcholine diffuses across the synaptic cleft and binds with receptors on the muscle cell surface membrane causing it to depolarise
• the action potential travels into the fibre through a system fo T-tubules that are extensions of the cell surface membrane and branch throughout the cytoplasm of the muscle (the sarcoplasm)
• the tubules are in contact with the endoplasmic reticulum of the muscle which has actively transported calcium ions from the cytoplasm of the muscle leading to a low concentration of calcium ions in the cytoplasm
• the action potential opens the calcium ion protein channels on the endoplasmic reticulum and calcium ions diffuse into the muscle cytoplasm down a concentration gradient
• the calcium ions cause the tropomyosin molecules the were blocking the actin binding sites to pull away
• ADP molecules attach to the myosin heads so now they are in a state to bind to actin filaments forming cross-bridges
• once attached to the actin filament the myosin heads change their angle pulling the actin filament along as they do so and releasing a molecule of ADP
• an ATP molecule attaches to each myosin head causing it to become detached from the actin filament
• the calcium ions activate the enzyme ATPase which hydrolyses ATP to ADP. This provides the energy for the myosin head to return to its original position
• the myosin head with an attached ADP molecule then reattaches itself further along the actin filament and the cycle is repeated as long as the concentration of calcium ions in the myofibril remains high
• when nervous stimulation ceases the calcium ions are actively transported back into the endoplasmic reticulum using energy from the hydrolysis of ATP
• the reabsorption of the calcium ions allows tropomyosin to block the actin filament binding sits
• myosin heads are now unable to bind to actin filaments and contraction ceases

So this all requires A LOT of energy. This is supplied by the hydrolysis of ATP to ADP + Pi. This energy is needed for the movement of myosin heads and the reabsorption of calcium ions into the endoplasmic reticulum by active transport. In an active muscle there is a great demand for ATP. Most energy is regenerated from ADP during the respiration of glucose in the mitochondria but this requires oxygen. In very active muscles we can rapidly generate ATP anaerobically using phosphocreatine

3.6.2.1 Nerve impulses

Neurones are specialised cells adapted to carry electrochemical changes (nerve impulses) from one part of the body to another. A myelinated motor neurone is made up of:

• a cell body containing the usual organelles including a large amount of RER which is associated with the production of proteins and neurotransmitters
• dendrons which are extensions of the cell body which subdivide into dendrites that carry nerve impulses towards the cell body
• an axon which is a single long fibre that carries nerve impulses away from the cell body
• Schwann cells which surround the axon protecting it providing electrical insulation. They also carry out phagocytosis
• A myelin sheath which forms a covering to the axon and is made up of the membranes of the Schwann cells
• nodes of Ranvier are constrictions between adjacent Schwann cells where there is no myelin sheath

Resting potential

The inside of an axon is negatively charged relative to the outside. This is a resting potential and in this condition the axon is said to be polarised and this can be established due to the following events:

• sodium ions are actively transported out of the axon by the sodium-potassium pump
• potassium ions are actively transported into the axon by the sodium-potassium pump
• the active transport of sodium ions is greater than the active transport of potassium ions so an electrochemical gradient is established
• the sodium ions begin to diffuse back in while the potassium ions begin to diffuse back out
• most of the gates in the channels that allow potassium through are open whilst most of the gates in the channels that allow sodium ions to move through are closed

When a stimulus is detected by a receptor it causes a temporary reversal of the charges either side of the axon. If the stimulus is large enough the inside of the membrane becomes a positive charge. This is known as an action potential and the axon membrane is now said to be depolarised. This occurs because the voltage-gated channels change shape opening/closing depending on the voltage across the membrane:

1. at resting potential some potassium voltage-gated channels are open (the permanently open ones) but the sodium voltage-gated channels are closed
2. the energy of the stimulus causes some sodium voltage-gates channels to open causing sodium ions to diffuse into the axon through these channels along an electrochemical gradient. This triggers a reversal in the potential difference across the membrane as they are positively charged
3. as sodium move in more sodium channels open causing a greater influx (this is positive feedback)
4. once an action potential of ~40mV is established the voltage gates on the sodium channels close to prevent further influx of sodium ions and the voltage gates in potassium channels begin to open
5. lots of potassium ions diffuse out causing more potassium ions to diffuse out starting repolarisation of the axon
6. the outward diffusion of the potassium ions causes a temporary overshoot of electrical gradient with the axon inside being more negative relative to the outside than usual (hyperpolarisation). The potassium ion channels close and the sodium potassium pump causes sodium to move out and potassium to move in reestablishing the resting potential. The axon is said to be repolarised.

Once created the action potential moves rapidly along the axon. As one region of the axon produces an action potential and depolarises it acts as a stimulus for the depolarisation of the next region of the axon. The action potential is a wave of depolarisation and the previous region of the membrane returns to its resting potential by undergoing repolarisation.

How an action potential moves along an unmyelinated axon:

• at resting potential the axon membrane is polarised and negatively charged on the inside relative to the outside
• a stimulus causes an influx of sodium ions and hence a reversal of charge on the axon membrane. This is the action potential and the membrane is depolarised
• the localised electric currents established by the influx of sodium ions cause the opening of sodium voltage-gated channels a little further along resulting in depolarisation in that region. Behind this region sodium channels close and potassium channels open beginning repolarisation
• the action potential is propagated in the same way further along the axon
• repolarisation allows sodium ions to be actively transported out and potassium ions to be actively transported in returning the axon to its resting potential

How an action potential moves along a myelinated sheath: In myelinated axons the sheath of myelin acts as an electrical insulator preventing action potentials from forming. At intervals there are breaks in the insulation (nodes of Ranvier). Action potentials can occur at these points and so the action potential effectively jumps from node to node in a process known as saltatory conduction. An action potential travels along a myelinated  neurone faster than along the axon of an unmyelinated one of the same diameter.

The transmission of an action potential along the axon of a neurone is the nerve impulse. A number of factors affect the speed at which an action potential passes along an axon:

• the myelin sheath
• the diameter of an axon - the larger the diameter the faster the speed
• temperature - this affects the rate of diffusion of ions so a higher temperature means a faster nerve impulse

Once an action potential has been created in any region of an axon there is a period after where inward movement of sodium ions is prevented as the sodium voltage-gated channels are closed. During this time it is not possible for a further action potential to be generated. This is known as the refractory period. It has 3 purposes:

• ensures action potentials are propagated in one direction only as action potentials cannot be propagated in a region of refractory
• produces discrete impulses as a new action potential cannot be formed immediately behind the first one ensuring action potentials are separated from one another
• it limits the number of action potentials as they are separated from one another

3.6.1.1 Survival and response

A stimulus is a detectable change in the internal/external environment of an organism that leads to a response in the organism. This increases the organisms chance of survival (e.g the ability to detect and move away from prey, or detect and move towards a food source).

So we need to know quite a bit about plants (in particular, flowering plants). Plants have no nervous system so their responses to external stimuli involve hormone-like substances known as plant growth factors. They are produced in small quantities and an example is IAA which is an auxin. IAA controls plant elongation. Growth factors can move from growing regions to other tissues (meaning that they are not confined to the tissue they were produced in) and bring about a change in growth in the following way:

1. Cells in the shoot tip produce IAA
2. the IAA is transported down the shoot evenly throughout all regions
3. Light causes the movement of IAA from the light side to the shaded side of the shoot so a greater concentration of IAA builds up on the shaded side
4. The cells on the shaded side elongate more as there is a greater concentration of IAA here
5. The shaded side elongates faster than the light side which causes the shoot tip to bend towards the light

IAA inhibits root growth:

1. Cells in the root tip produce IAA
2. the IAA is transported initially to all sides of the root
3. Gravity influences the movement of IAA from the upper side to the lower side
4. A greater concentration builds up on the lower side meaning the cells here elongate less than those on the upper side
5. This causes the root to bend down towards gravity.

IAA has a number of effects on plant cells including increasing the plasticity of their cell walls. This response only occurs in young cell walls where cells are able to elongate. As cells mature they develop greater rigidity meaning that older parts of the shoot/root will not respond. The acid growth hypothesis is the current way in which we think IAA increases the plasticity of cells. It involves the active transport of hydrogen ions from the cytoplasm into the cell walls causing the cell wall to become more plastic allowing the cell to elongate.

A taxis is a simple response whose direction is determined by the direction of the stimulus. As a result a motile organism responds directly to the environmental changes by moving away from an unfavourable one. Taxis are classified according to whether the movement is towards (positive) or away from (negative taxis) the stimulus and by the nature of the stimulus. Some examples are as follows:

• Positive phototaxis - single celled algae move towards light to increase their chances of survival as they are photosynthetic
• Positive chemotaxis - some bacteria move towards a region of high glucose concentration. This increases their chance of survival because they use glucose as a food source.

A kinesis is a form of response in which the organism does not move towards or away from a stimulus. Instead it changes its speed and also the rate it changes direction. If it crosses a line between favourable and unfavourable conditions its rate of turning increases which raises its chances of quickly returning to a favourable environment. If it has moved a considerable distance in an unfavourable environment its rate of turning decreases so it moved in a long straight line before sharply turning as this is likely to bring the organism into a new region with favourable conditions.

A tropism is the growth of part of a plant in response to a directional stimulus. The type of response is named after the stimulus and the direction the organism moves relative to it. Examples include:

• positive phototropism - plant shoots grow towards the light so their leaves are in a more favourable position for photsynthesis
• Plant roots grow away towards gravity (positive gravitropism). This increases their probability to find water and mineral ions.

Stimuli are detected by receptors which are specific to one type of stimulus. A coordinator formulates a suitable response, which is produced by an effector. Animals also have a nervous system in addition to hormonal communication. This has many different receptors and effectors which are linked to a central coordinator.

The spinal cord is a column of nervous tissue running along the back which lies inside the vertebral column for protection. Pairs of nerves emerge at intervals along the spinal cord. A reflex is rapid, short-lived, and localised. The pathway of neurones involved is known as a reflex arc:

1. stimulus 
2. receptor
3. sensory neurone
4. relay neurone/coordinator
5. motor neurone
6. effector
7. response

Reflex actions are important as they make survival more likely. They are important for the following reasons:

• involuntary so do not require the decision powers of the brain so the brain is free to carry out more complex responses
• they protect the body from harm and are effective from birth so do not have to be learnt
• they are fast as the neurone pathway is short with very few synapses
• the absence of the decision making process also makes it fast

3.6.4.1 Principles of homeostasis and negative feedback

Homeostasis in mammals involves physiological control systems that maintain the internal environment within restricted limits. It is very important for many reasons, including:

• enzymes (e.g those involved in biochemical reactions within cells/other proteins such as channel proteins are sensitive to changes in pH and temperature). Any changes from the optimum reduce the rate of reaction and, if severe enough, may denature the enzyme and the reaction will cease altogether. Maintaining a fairly constant environment means that reactions take place at a suitable rate.
• Changes to the water potential of blood/tissue fluid may cause cells to shrink/expand as a result of water leaving/entering via osmosis. This means the cells cannot operate normally.
• The maintenance of a constant blood glucose concentration is essential to ensure a constant water potential. A constant blood glucose concentration also ensures a reliable source of glucose for respiration by cells.

Positive feedback

This occurs when a deviation from an optimum causes changes that result in an even greater deviation from the normal. As example occurs in neurones where a stimulus leads to a small influx of sodium ions (this increases the permeability of the neurone membrane to sodium ions and more ions enter).


Negative feedback
Negative feedback is when the change produced by the control system leads to a change in the stimulus detected y the receptor and turns the system off. This restores systems to their original level. 


Control of any system involves a series of stages:

• the optimum point
• a receptor
• a coordinator
• an effector
• a feedback mechanism

The possession of separate mechanisms involving negative feedback controls departures in different directions from the original state, giving a greater degree of homeostatic control as the return to the optimum can be brought about faster.

For example, if there is a fall in blood glucose concentration this is detected by receptors on the cell-surface membrane of alpha cells in the pancreas. These secrete glucagon which causes liver cells to convert glycogen to glucose to raise the blood glucose concentration. There is now reduced stimulus so the secretion of glucagon reduces.

If blood glucose concentration rises insulin will be produced from beta cells in the pancreas. Insulin increases the uptake of glucose by cells (it is converted to glycogen and fat). There is now reduced stimulus so the production of insulin reduces.

3.6.2.2 Synaptic transmission

The point where one neurone ends and communicates with another/an effector is known as a synapse. Synapses transmit information from one neurone to another by means of chemicals (known as neurotransmitters). In between each neurone is a little gap known as the synaptic cleft in which the first neurone (the presynaptic neurone) releases the neurotransmitter into. Here, the axon is slightly swollen and termed the synaptic knob (this is at the end of the presynaptic neurone). The presynaptic knob contains synaptic vesicles (which the neurotransmitter is stored in), many mitochondria and endoplasmic reticulum (as these are required to  manufacture the neurotransmitter in the axon). The neurotransmitter is released from the synaptic knob into the synaptic cleft where it diffuses across the cleft to the post synaptic neurone which receives it with the help of specific receptor proteins on its membrane - synapses that produce new action potentials in this way are known as excitatory synapses. Synapses can only pass information in one direction only (they are unidirectional) - from the presynaptic neurone to the postsynaptic neurone. 

Summation:
Low frequency action potentials may lead to insufficient concentrations of a neurotransmitter which will not trigger a new action potential in the postsynaptic neurone. This can be overcome by the rapid build up of neurotransmitter in the synapse by summation in one of two methods:

• Spatial summation involves a number of different presynaptic neurones releasing enough neurotransmitter to exceed the threshold value to trigger a new action potential in one postsynaptic neurone
• Temporal summation involves a single presynaptic neurone releasing a neurotransmitter many times over a short period. A new action potential is triggered if the overall concentration of neurotransmitter exceeds the threshold value of the postsynaptic neurone.

Inhibition: 

It is also possible for synapses to make it less likely that a new action potential will be created on the postsynaptic neurone (these are inhibitory synapses):

• The presynaptic neurone releases a type of neurotransmitter that binds to chloride ion protein channels on the postsynaptic neurone
• The neurotransmitter causes the chloride ion protein channels to open and chloride ions move into the postsynaptic neurone (by facilitated diffusion)
• The binding of the neurotransmitter causes potassium protein channels to open and potassium moves out of the post synaptic neurone into the synapse
• the effect of the negatively charged chloride ions moving in and the potassium ions moving out make the inside of the postsynaptic membrane more negative (and the outside more positive)
• The membrane potential increases
• this causes hyperpolarisation making it less likely that a new action potential will be created as a larger influx of sodium ions is needed to produce an action potential

Cholinergic synapse vs neuromuscular junction 

So we need to be able to compare the transmission across a cholinergic synapse and a neuromuscular junction...

Cholinergic synapses

A cholinergic synapse is a synapse in which acetylcholine is the neurotransmitter:

• An action potential arrives at the end of the presynaptic neurone. This causes calcium ion protein channels to open and calcium ions to enter the synaptic knob (facilitated diffusion)
• This influx of calcium ions into the presynaptic neurone causes synaptic vesicles to fuse with the presynaptic membrane and release acetylcholine into the synaptic cleft
• Acetylcholine molecules diffuse across the narrow synaptic cleft and bind to receptor sites on sodium ion protein channels in the postsynaptic neurone membrane
• This causes sodium ion protein channels to open and sodium ions diffuse in rapidly (facilitated diffusion)
• This influx of sodium ions generates a new action potential in the postsynaptic neurone
• Acetylcholinesterase hydrolyses acetylcholine into choline and acetyl (ethanoic acid) which diffuse back across the synaptic cleft into the presynaptic neurone. This also prevents the continuous generation of an action potential in the post synaptic neurone
• ATP released from mitochondria is used to recombine choline and acetyl (ethanoic acid). The acetylcholine is stored in synaptic vesicles for future use
• Sodium ion protein channels close

Cholinergic synapse structure/function:

• has neurotransmitters that are transported by diffusion
• has receptors that cause an influx of sodium ions upon binding with the neurotransmitter
• uses a sodium-potassium pump to repolarize the axon
• uses enzymes to break down the neurotransmitter
• can be excitatory or inhibitory
• links neurone-neurone or neurone-effector organ
• Motor neurones, sensory neurones, and intermediate neurones may be involved
• a new action potential may be produced along the post synaptic neurone
• acetylcholine binds to receptors on the membrane of the postsynaptic neurone

Neuromuscular junctions

This is the point where a motor neurone meets a skeletal muscle fibre. There are many junctions along the muscle to allow the whole muscle to contract at the same time. All muscle fibres supplied by a single motor neurone act together as a unit known as a motor neurone. This means we can control how much force the muscle exerts - e.g if we only want a light force we only stimulate a few units:

• A never impulse is received at the neuromuscular junction and the synaptic vesicles fuse with the synaptic membrane
• Acetylcholine is released into the synaptic cleft and diffuses across to the post synaptic membrane (this is the membrane of the muscle)
• This alters the membranes permeability to sodium ions and sodium ions enter rapidly which depolarizes the membrane
• Acetylcholinesterase hydrolyses acetylcholine into choline and acetyl (ethanoic acid) which diffuse back across the synaptic cleft into the presynaptic neurone. This ensures that the muscle is not over stimulated.

Neuromuscular junction synapse structure/function:

• has neurotransmitters that are transported by diffusion
• has receptors that cause an influx of sodium ions upon binding with the neurotransmitter
• uses a sodium-potassium pump to repolarize the axon
• uses enzymes to break down the neurotransmitter
• only excitatory
• only links neurone-muscle
• only motor neurones are involved
• the action potential ends here
• acetylcholine binds to receptors on the membrane of the muscle fibre

3.6.1.3 Control of heart rate

Nervous organisation
Okay so I can't actually find this in the spec so feel free to skip it out, but there's a little bit about it in my textbook which I've found pretty useful to know for answering exam Qs etc. It basically lets us know about how the nervous system is split up...

So overall we have the nervous system. This has two major divisions:

• the central nervous system (CNS) made up of the brain and spinal cord
• the peripheral nervous system (PNS) made up of pairs of nerved that originate from either the brain or spinal cord. this can be divided into two further subdivisions:
• sensory neurones which carry electrical signals in the form of nerve impulses from receptors towards the central nervous system
• motor neurones which carry nerve impulses away from the CNS to effectors. The motor nervous system can again be divided into two more divisions:
• The voluntary nervous system carries nerve impulses to body muscles and is under conscious/voluntary control
• The autonomic nervous system controls our subconscious/involuntary activities and carries nerve impulses to internal muscles (cardiac and smooth muscle) and glands. You know what's coming... it can be broken down into two more nervous systems which work antagonistically:
• the sympathetic nervous system stimulates effectors therefore speeds up any activity. It helps us to cope with stressful situations thanku sympathetic nervous system) by heightening our awareness and preparing us for activity - many also studying psychology will know this as the flight or fight response.
• the parasympathetic nervous system inhibits effectors and therefore slows down any activity. It controls activity under normal resting conditions (when you're not stressed or anything) and is concerned with conserving energy and replenishing the body's reserves.

Control of the heart rate

Okay so I wanted to get all that said above because basically the activities of internal glands/muscles are regulated by the balance of the sympathetic and parasympathetic nervous systems and control of the heart rate is a good example of this.

Cardiac muscle is myogenic (contraction is initiated within the muscle as apposed to by the nervous system (neurogenic)). In the wall of the right atrium sits a group of cells that are collectively known as the SAN (sinoatrial node) - here the initial stimulus for contraction originates. This has a basic rhythm of stimulation that determines the heart beat rate. The sequence of events that leads to a heartbeat is as follows...

• A wave of electrical excitation spreads out from the SAN across both atria causing them to contract
• A layer of non-conductive tissue prevents the wave crossing to the ventricles. This is known as the atrioventricular septum
• The wave of excitation enters the AVN (atrioventricular node) - a second group of cells which lie between the atria
• After a short delay, this conveys a wave of electrical excitation between the ventricles along a series of specialised muscle fibres (Purkyne tissue) which make up the bundle of His
• The bundle of His conducts the wave through the atrioventricular septum to the base of the ventricles where the bundle branches into smaller fibres of the Purkyne tissue
• The wave of excitation is released from the Purkyne tissue causing the ventricles to contract quickly at the same time from the bottom of the heart upwards

We must of course be able to alter this heart rate e.g if we are running away from our parents. Changes to he heartrate are controlled by the medulla oblongata (a part of the brain). It has two centres. Which centre is stimulated depends on the nerve impulse they receive from two types of receptor which can respond to chemical or pressure changes within the blood:

• one increases heart rate linked to the sinoatrial note by the sympathetic nervous system
• one decreases heart rate linked to the sinoatrial node by the parasympathetic nervous system

Chemoreceptors are found in the wall of carotid arteries. They are sensitive to blood pH changes that result from CO2 concentration changes (more CO2 lowers the pH of blood as CO2 is acidic in solution):

• When the blood has a higher than usual CO2 concentration ifs pH lowers
• chemoreceptors in the walls of carotid arteries detect this and increase the frequency of nerve impulses to the centre in the medulla oblongata
• this centre increases the frequency of impulses via the sympathetic nervous system to the sinoatrial node
• this increases the rate of production f electrical waves by the SAN which increases the heart rate
• the increased blood flow causes more CO2 to be removed by the lungs so CO2 concentration returns to normal
• pH of the blood rises to normal and the chemoreceptors reduce the frequency of the nerve impulses to the medulla oblongata and the medulla oblongata reduces the frequency of impulses to the sinoatrial node which therefore leads to a reduction in heart rate

Pressure receptors occur in the walls of carotid arteries and the aorta:

• when blood pressure is lower than normal pressure receptors transmit more nervous impulses to the medulla oblongata. The medulla oblongata increases the frequency of impulses via the sympathetic nervous system to the SAN which increases the rate at which the heart beats
• when blood pressure is higher than normal pressure receptors transmit more nervous impulses to the medulla oblongata. The medulla oblongata increases the frequency of impulses via the parasympathetic nervous system to the SAN which decreases the rate at which the heart beats

You can calculate cardiac output using the following equation...

cardiac output = heart rate x stroke volume

3.6.1.2 Receptors

A receptor responds to a specific type of stimulus. The central nervous system receives sensory information through receptors.

Sensory reception = the function of these receptors
Sensory perception = the understanding/making sense of the information from receptors.


The Pacinian corpuscle
Okay so we need to know quite a it about the Pacinian corpuscle - this is just one type of receptor that responds to changes in mechanical pressure. they are most abundant on toes/fingers//the hand/soles of the feet/genitalia but also occur in joints/tendons/ligaments to enable the organism to know which joints are changing direction. It is specific (ie it will not respond to other stimuli, such as a change in light/heat/sound). It also produces a generator potential by acting as a transducer. In fact, all receptors do both of these. All stimuli involve a change of energy. The receptor (acting as a transducer) converts the energy into a nerve impulse known as a generator potential.

The structure of the Pacinian corpuscle:
It contains a single sensory neurone at the centre of many layers of tissue. Each layer is separated by a little bit of gel. the sensory neurone here contains stretch-mediated sodium channels (whose permeability to sodium ions changes when stretched/deformed - makes sense tbh).

Function of the Pacinian corpuscle:

1. In it's resting/usual state the stretch-mediated sodium channels are closed (well, they're not strictly closed but they're too narrow to allow sodium ions to pass along them. The Pacinian corpuscle has a resting potential (this refers to its potential difference/voltage).
2. Pressure is applied
3. The Pacinian corpuscle is deformed and the membrane around the neurone is stretched
4. The stretch-mediated sodium channels open
5. Sodium ions diffuse into the neurone via facilitated diffusion
6. The potential of the membrane changes due to the influx of sodium ions
7. This produces a generator potential
8. The generator potential creates an action potential (if it is above threshold value)

The human retina

The retina holds the light receptor cells of our eyes (rods and cones are the two main types, you might have come across these at GCSE). As all receptors do, they convert the energy from the stimulus into the electrical energy of a nerve impulse (in this case the stimulus is light).

Rod cells:

• Rod shaped
• Absent at the fovea but plentiful at the periphery of the retina
• Cannot distinguish different wavelengths of light therefore only see black and white.
• More numerous than cone cells (~120 million per eye)
• Used to detect low level/dim light
• As per usual, a certain threshold value must be exceeded before a generator potential is created in the bipolar cells to which they are created. Many rod cells are connected to a single sensory neurone in the optic nerve. This means that there is a greater chance that the threshold value is exceeded as a number of rod cells are connected to each bipolar cell = summation (this is known as retinal convergence).
• Rhodopsin must be broken down to create a generator potential (this is the pigment in the cells) - there is enough energy in low light to break down this pigment hence rods let us see in low light.
• There is a downside, since many rods are connected to one bipolar cell (which is good as it means summation/retinal convergence) it means that light received by many rods that are all connected to one bipolar cell will only produce one nerve impulse so the brain cannot distinguish between separate sources of light e.g there is low resolution (this means poor visual acuity and is why things might look a little sort of blurry in the night).

Cone cells:

• Cone shaped
• Fewer at the retinal periphery but plentiful at the fovea
• Three different types which all respond to different wavelengths of light = images can be perceived in full colour
• Less numerous than rod cells (~6 million per eye)
• Detect brighter light
• Often connected to just one bipolar cell meaning that stimulation is not combined to exceed a threshold value - so only light of a high intensity produces a generator potential.
• Iodopsin must be broken down - each of the three types of cone cells contains a specific type of iodopsin. Only light of high intensity will break down iodopsin and create a generator potential.
• Since each cone cell is connected to its own bipolar cell, if two adjacent cones are stimulated two nerve impulses will be received by the brain (this means high resolution so good visual acuity)

The fovea

Okey so a little bit about the fovea. So basically the lens of the eye focuses light on the part of the retina that is opposite the pupil - this is the fovea. This means that the fovea gets the highest intensity of light hence lots of cone cells and not many rod cells are situated there. Where there is lower light intensity 9the retinal periphery) lots of rod cells are situated.