Chapter 13

As species have evolved cells within organisms have become specialised to peform specific functions and as a result need to coordinate the function of different cells and systems to operate effectively. In many multicellular organisms the functions of organs must be coordinated in order to maintain a relatively constant internal environment, this is known as homeostasis. Nervous and hormonal coordination rely on communication at a cellular level through cell signalling. This occurs through one cell releasing a chemical which has an effect on a target cells, through this oricess singals can be transferred locally such as a neurotransmitter, or signals can be transferred across large distances using hormones such as ADH. 

The nervous system is responsible for detecting changes in the internal and external environment. Neourones transmit electrical impulses rapidly around the body so that the organism can respond to stimuli, there are several types of neurones that work together to carry information detected by sensory receptors to the effecter to carry out an appropriate response.

Structure of a neurone:

• Cell body - this contains the nucleus surrounded by cytoplasm which has large amounts of ER and mitochondria involved in the production of neurotransmitters.
• Dendrons - these are short extensions which come from the cell body, these divide into smaller branches called dendrites which are responsible for transmitting electrical impulses towards the cell body.
• Axons - these are singular, elongated nerve fibres that transmit impulses away from the cell body, these fibres can be very long such as those from the toes to the spinal cord. The fibre is cylindrical in shape and has a very narrow region of cytoplasm surrounded by a plasma membrane.

Neurones can be divided into 3 groups according to their function:

• Sensory neurones - these transmit impules from a sensory receptor cell to a relay neurone, motor neurone or the brain. They have one dendron which carries the impulse to the cell body and one axon that carries the impulse away from the cell body.
• Relay neurones - these neurones transmit impulses between neurones, for example between sensory and motor neurones, they have many short axons and dendrons.
• Motor neurones - these neurones transmit impulses form a relay neurone or sensory neurone to an effector such as a muscle or gland, they have one long axon and many short dendrites.

Myelinated neurones: The axons of some neurones are covered in a myelin sheath, made of many layers of plasma membrane. Schwann cells produce these layers of membrane by growing around the axon many times, and each time they do another phospholipid bilayer is laid down. The sheath acts as an insulating layer and allows these neurones to conduct electrical impulses at a much faster speed. Between each adjacent Schwann cell there is a small gap known as the node of ranvier, and due to the insulating properties of the sheath the impulse jumps from one node to the next rather than continuously along the fibre.

Sensory receptors convert the stimulus they detect into an electrical impulse which is then passed on to the central nervous system and then a response is coordinated in the brain. All sensory receptors are specific to a single type of stimulus, and act as a tranducer. Detection of light, heat sound or pressure is converted into a nervous impulse called a generator potential.

Pacinian corpuscles are specific sensory receptors that detect mechanical pressure and are located deep within the skin and within joints. The end of the sensory neurone is found within the centre of the corpuscle surrounded by layers of connective tissue each seperated by a layer of gel. Within the membrane of the neurone are sodium ion channels which are stretch mediated channels in this case, and their permeability to sodium ions changes when they change shape. In its normal state the stretch mediated sodium ion channels are too narrow to allow sodium ions to pass through them, so the neurone of the pacinian corpuscle has a resting potential. When pressure is applied the corpuscle changes shape, causing the membrane surrounding its neurone to stretch, which results in the widening of the sodium channels so the iosn can diffuse into the neurone, resulting in the depolarisation of the neurone resulting in a generator potential and in turn an action potential that passes along the sensory neurone that will be transmitted to the CNS.

When a neurone is not transmitting an impulse the potential difference across the membrane (between the inside and outside of the axon) is known as the resting potential, in this state the outside of the membrane is more positively charged than the inside of the axon, and the membrane is said to be polarised as there is a potential difference across it, it is normally about 70mV. The resting potential occurs as a result of the movement of sodium and potassium ions across the axon membrane. The phospolipid bilayer prevents these ions from diffusing across the membrane and so they have to be transported via channel proteins. Some of these are gated whilst others remain open all the time. The following results in the creation of a resting potential:

• Sodium ions are actively transported out of the axon whilst potassium ions are actively pumped into the axon by the intrinsic protein known as the sodium-potassium pump. For every 3 sodium ions pumped out two potassium ions are pumped in.
• This results in an electrochemical gradient where sodium ions diffuse back into the axon and potassium ions diffuse out of the axon, however most of the gated sodium ion channels are closed whilst potassium ones are open, resulting potassium ions diffusing out of the axon, so the outside of the membrane becomes more positively charged, resulting the relative negative charge of -70mV across the membrane, with the inside negative relative to the outside.

When a stimulus is detected by a sensory receptor the energe of the stiumuls temporarily reverses the charges of the axon potential resulting in depolarisation where the charge across the membrane becomes about + 40mV. As the impulse passes repolarisation then occurs and the neurone returns to its resting potential. An action potential occurs when when protein channels in the axon membrane change shape as a result of the change of voltage causing them to open or close. There a several stages of an action potential:

• The neurone has a resting potential, some potassium ion channels are open but sodium ion voltage gated channels are closed.
• The energy of the stimulus triggers some sodium ion voltage gated channels to open resulting in sodium ions diffusing into the axon down their electrochemical gradient.This change in charge causes more sodium channels to open, through positive feedback
• When the potential difference reaches around +40mV the sodium voltage gated channels close and and the voltage gated potassium ion channels open, and potassium ions diffuse out of the axon down their electrochemical gradient resulting in repolarisation and reducing the charge.
• Initially the loss of potassium ions results in the inside of the axon being more negative than resting potential in hyperpolarisation, now only the pump os active, returning the axon to its resting potential

A nerve impulse is an action potential that starts at one end of the neurone and is propagated along the axon to the other end of the neurone. The initial stimulus causes a change in the sensory receptor so the first region of the axon membrane is depolarised, acting as a stimulus for the depolarisation of the next region in a wave continuing along the the axon as once sodium ions are inside the axon they are attracted to the negative charge ahead and the concentration to diffuse further along the axon. The localised electrical circuits established by the influx of sodium iosbs causes the opening of sodium ion voltage gated channels further along the axon causing depolarisation in the next region, whilst the one behind begins to repolarise as its sodium voltage gated channels close and potassium ions begin to leave down their electrochemical gradient and this wave continues along the axon with repolarisartin following it in return to resting potential. After an action potential there is a short period of time when the axon cannot be excited again known as the refractory period where voltage gated sodium ion channels remain closed preventing the creation of an action potential. This prevents the propagation of an action potential bakcwards along the axon as well as forwards and ensuring that action potentials are unidirectional, it also ensures they are discrete and that action potentials do not overlap.

Myelinated axons transfer electrical impulses much faster than non-mylelinated axons which is because the depolarisation of the axon membrane can occur at the Nodes of Ranvier where no myelin is present as only here can sodium ions pass through the protein channels in the membrane, causing longer localised circuits between the nodes. This causes the action potential to jump from one node to another in a process called saltatory conduction, and is much faster than a wave of depolarisation along the whole length of the axon membrane, so by reducing the number of places where channels open and ions move in speeds up the transmission, and long term it is more energy efficient, as repolarisation uses ATP in ths sodium pump so by reducing the amount of repolarisation needed saltatory conduction makes the conduction of impulses more efficient. Apart from myelination the speed at which an action potential travels can be effected by the axon diameter, as there will be less resistance to the flow of ions in the cytoplasm in a larger axon, and th temperature, as higher temperatures will increase the rate of diffusion of ions but only to a certain point as after this the sodium-potassium pump enzymes will denature.  Nerve impulses are said to be all or nothing responses as a certain level of stimuus (threshold value) always triggers a response, or no response if the threshold value is not reached. No matter how large the stimulus is the same sized action potential will always be triggered. The size of the stimulus will only affect the number of action potentials generated in a given time - the larger the stimulus the more frequently action potentials are generated.

Impulses often need to be passed between several neurones, the junction between two neurones is called a synapse, and impulses are transmitted between these using neurotransmitters. All synpases have a number of key features:

• Synaptic cleft - the gap which seperates the axon of one neurone to the dendrite of the next.
• Presynaptic neurone - neurone along with the impulse has arrived.
• Synpatic knob - the swollen end of the presynaptic neurone, it contains many mitochondria and large amounts of ER to enable the manufacture of neurotransmitters.
• Synpatic vesicles - besicles containing neurotransmitters which fuse with the presynpatic membrane and release their contents into the synaptic cleft.
• Neurotransmitter receptors - receptor molecules which the neurotransmitter binds to in the postsynaptic membrane.

Neurotransmitters can be grouped into 2 catergories:

• Excitatory - these result in the depolarisation of the postsynaptic neurone and trigger an action potential if threshold value is reached, eg acetylcholine.
• Inhibitory - these result in the hyperpolarisation of the postsynaptic membrane and prevent an action potential from being triggered, eg GABA.

Synaptic transmission occurs as the result of the following:

• The action potential reaches the end of the presynaptic neurone and depolarisation of the presynaptic membrane causes calcium ion channels to open.
• This causes synpatic vesicles containing neurotransmitters to fuse with the presynaptic membrane and neurotransmitter is released into the synpatic cleft via exocytosis.
• Neurotransmitter diffuses across the cleft and binds with its specific receptor molecule on the postsynaptic membrane, causing sodium channels to open.
• Sodium ions then diffuse into the postsynaptic neurone triggering an action potential and the impulse is propagated along the postsynaptic neurone/

Once a neurotransmitter has triggered an action potential it is important that it is removed so that the stimulus is not maintained so another stimulus can arrive and affect the synapse. so any neurotransmitter left in the synpatic cleft is broken down by enzymes also released from the receptors on the postsynaptic membrane and the products are taken back to the presynaptic knob to reform the neurotransmitter. Removing the neurotransmitter from the synaptic cleft prevents the response from happening again and allows the neurotransmitter to be recycled.

Cholinergic synapses use the neurotransmitter acetylcholine (ACT) and are common in neuromuscular junctions where a motor neurone reaches a muscle cell, so if ACT reaches the receptors on a muscle cell it will cause the muscle to contract. The arrival of an action potential at the end of the presynaptic neurone cayses calcium ion channels to open and calcium ions toi diffuse into the synaptic knob, causing the synaptic vesicles to diffuse to fuse with the presynaptic membrane and release ACT into the synaptic cleft which then diffuses across the cleft ans binds to receptor sites on the sodium ion channels in the membrane of the postsynaptic neurone, causing sodium ions to rapidly diffuse in down a concentration gradient as the sodium ion channels open, generating a new action potential in the postsynaptic neurone or msucle cell. Once an action potential has been triggered ACT is hydrolysed by the specific enzyme acteylcholinesterase (ACTesterase) which is situated on the post synaptic membrane. ACT is broken down to ehtanoic acid and choline, which then diffuse back across the synaptic cleft and into the presynaptic neurone. ATP released by mitochondria is used to recombine choline and ethanioc acid into ACT and is stored in vesicles, recycling the neurotransmitter. Sodium ion channles close in the absence of ACT in the receptor sites preventing the continuous generation of a new action potential in the postsynaptic neurone.

• They ensure impulses are unidirectional. As the neurotransmitter receptors are only present on the postsynaptic membrane impulses can only travel from the presynaptic neurone.
• They can allow an impulse from one neurone to be transmitted to a number of neurones at multiple synpases, resulting in a single stimulus creating several simultaneous responses.
• A number of neurones can also feed into one synapse with a sinlge postsynaptic neurone resulting in stimuli from different receptors interacting to produce a single result.

Each stimulus form a presynaptic neurone causes the release of the same amount of neurotransmitter into the synapse, but in some cases this isn't enough to trigger an action potential, but if the amount of neurotransmitter builds up sufficiently it can reach the threshold value, this is known as summation:

• Spatial summation - this occirs when a number of presynaptic neurones connect to one postsynaptic neurone, each releasing neurotransmitter which builds up to a high enough level to trigger an action potential.
• Temporal summation - this occirs when a single presynaptic neurone releases neurotransmitter several times over a short period as a result of a maintained stimulus, this builds up in the synapse until the quantity is sufficient to trigger an action potential.

Many recreational and medical drugs cause their effects by acting on synapses which can cause inhibition or stimulation. Drugs that stimulate the nervous system create more action potentials in postsynaptic neurones resulting in an enhanced response, such as by:

• Mimicking the shape of the neurotransmitter - nicotine is the same shape as ACT, it can therefore bind to ACT receptors on the postsynaptic membrane and trigger an actio potential.
• Stimulating the release of more neurotransmitter, for example amphetamines.
• Inhibiting the enzyme responsible for breaking down the neurotransmitter in the synpase. For example nerve gas stops ACT from breaking down, resulting in loss of muscle control.

Drugs that inhibit the nervous systsem create fewer action potentials in postsynaptic neurones, resulting in a reduced response, these drugs may work by:

• Blocking receptors - this means the neurotransmitter can no longer bind and activate the receptor. For example curare blocks ACT receptors at neuromuscular junctions, so the muscle cannot be stimulated resulting in paralysis.
• Binding the specific receptors on the post synaptic membrane of some neurones and changing the shape of the receptors so the binding of the neurotransmitter increases. 

• Central nervous system (CNS) - this consists of your brain and spinal cord.
• Peripheral nervous system (PNS) - this consists of all the neurones that connect the CNS to the rest of the body. These are the sensory neurones which carry nerve impulses from receptors to the CNS, and the motor neurones which carry nerve impulses away from the CNS to the effectors.

• Somatic nervous system - this system is under conscious control and is uded when you voluntarily decided to do something, for example an impulse via the somatic system to a muscle when you decided to move it.
• Autonomic nervous system - this system works constantly and is under subconscious control and is used when the body does something involuntarily, for example causing the heart to beat or to digest food, the autonomic nervous system carries impulses to glands, cardiac and smooth muscle.
• The autonmic system is then further divided into the sympathetic and parasympathetic nervous system, if the outcome increases activity such as increasing heart rate it will involve the sympathetic nervous system, if the outcome decreases activity such as decreasing breathing rate after exercise it will involve the parasympathetic system.

An aduly human brain contains about 86 billion neurones, as the brain is responsible for processing all the information collected by receptor cells about changes in the external and internal environment. The advantage of having a central control centre for the whole body is that commication between the neurones is much faster than if the control centers for different functions were distributed around the body. The brain is protected by the skull and is surrounded by protective membranes called meninges. The main five areas are:

• Cerebrum - controls voluntary actions such as learning, memory and conscious thought.
• Cerebellum - controls unconscious functions such as posture and balance.
• Medulla oblongata - used in autonmic control, for example it controls breathing and heart rate.
• Hypothalamus - regulatory centre for temperature and water balance.
• Pituitary gland - stores and releases hormones that regulate homeostasis

Many different techniques can be used to study the brain, autopsies can be used to examine the actual structure, but at this stage the brain is alread dead, MRIs allow the brain to be studies during activity through areas with increased blood flow, and CT scans can create a series of detailed 3D x ray images.

Cerebrum: The cerebrum receives sensory information, interprets it using previous experiences and then sends impules along motor neurones to effectors. It is responsible for coordinating all of the body's voluntary responses as well as some involuntary ones. The cerebrum is highly convoluted increasing its surface area considerably and so its capacity for complex activity. It is split into left and right cerebral hemispheres, each of which controls one half of the body, the outer layer of each is called the cerebral cortex. The most sophisticated processes occur in the frontal and prefrontal lobe of the cerebral cortex. Each sensory area within each hemisphere recieves information from receptor cells located in sense organs, the size of which is proportional to the number of receptor body cells in that part. The information is then passed on to other sections of the brain to be analysed and acted on. Impulses come into motor areas where motor neurones send out impulses, the size of the motor area allocated is proportional to the number of motor endings in it. The main region whuch controls movement is the primary motor complex located at the back of the frontal lobe. In the base of the brain impulses from each side of the body cross, so as a result of this intergration of these inputs, for example from the visual cortex, the brain is able to judge distance and perspective.

Cerebellum: This area of the brain is concerned with the control of muscular movement, body posture and balance - it does not initiate it but coordinates it, so if this area of the brain is damaged a person will suffer from jerky movement. The cerebellum receives information from the organs of balance in the ears and information about the tone of muscles and tendons, it then relays this to the areas of the cerebral cortex that are involved in motor control.

Medulla oblongata: This contains many important regulatory centers of the autonomic nervous system, these control refelx activities such as ventilation and heart rate.

Hypothalamus: This is the main controlling region for the autonomic nervous system, and has two centres, one for the sympathetic system and one for the parasympathetic system, and has a number of functions such as controlling complex patterns of behaviour like sleepinf, monitoring the composition of blood plasma to maintain water and bloog glucose concentration, and producing hormones as it is an endocrine gland. 

Pituitary gland: This found at the base of the hypothalamus and controls most of the glands in the body. The anterior pituitary gland produces hormones such as FSH involved in growth abd reproduction.The posteriour pituitary stores, releases and produces hormones like ADH.

When the body is in danger it can respond to situations without conscious thought, causing a faster response minimising damage to the body. This is known as a reflex action. A reflex us an involuntary response to a senory stimulus. The pathway of neurones involved in a reflex action is known as a reflex arc. Most reflexes follow the same steps between the stimulus and response:

• Receptor - detectes stimulus and creates an action potential in the sensory neurone.]
• Sensory neurone - carries impulse to spinal cord.
• Relay neurone - connects the senory neurone to the motor neurone within the spinal cord or brain.
• Motor neurone - carries impulses to the effector to carry out the appropriate response.

The spinal cord is a column of nervous tissue running up the back and is surrounded by the spine for protection, at intervals along the spinal cord pairs of neurones are present.

Knee-jerk reflex: This reflex is commonly tested by doctors and is a spinal reflex - the neural circuit only goes up to the spinal cord and not the brain. When the leg is tapped just below the kneecap it stretches the patellar tendon and acts as a stimulus which initiated a reflex arc that causes the extensor muscle on top of the thigh to contract whilst simultaneously a relay neurone inhibits the motor neurone of the flexor muscle, causing it to relax, this contraction with the relaxation of the antagonistic flexor hamstring causs the leg to kick. This reflex is used by thr body to maintain posture and balance allowing you to remain balanced with little effort or conscious thought. The absence of this reflex may indicate nervous problems and may be a sign of a cerebellar disease.

Blinking reflex: This is ain involuntary blinking of the eyelids and occurs when the cornea is stimulated, and its purpose is to keep the cornea safe from damage due to foreing bodies, and this type of response is known as the corneal reflex. A blink reflex also occurs in response to hih intensity sound or light which is known as the optical reflex, and is cranial. When the cornea is irritated the stimulus triggers an impulse along the 5th cranial nerve, which passes through a relay neurone in the lower brain stem and impulses from there are sent along the branches of the motor 7th cranial nerve to initiate a motor response to close the eyelids, the reflex initiates a consensual response and both eyes are closed at the same time. This reflex can be tested on unconscious patients to see if the brain is functioning.

Reflexes are essential for survival as they avoid the body being harmed, or reduce the severity of any damage. For example in dim light the pupil expands due to the relaxing of the iris so you can take in as much light as possible, or the reverse in bright light to prevent damage to the retina. Reflexes may increase your chances of survival by:

• Being involuntary responses - the decision making regions of the brain are not involved, and therefore the brain is able to deal with more complex responses, and so it prevents the brain from being overloaded with situations in which the response is always the same.
• Not having to be learnt - they are present at birth and therefore provide immediate protection.
• Extremely fast - the reflex arc is very short and normally only involves one or two synapses, which are the slowest part of nervous transmission.
• Many reflexes are what we would consider everyday actions such as those keeping us upright, or those which allow us to digest food.

There are around 650 muscles in the body, there are three types of muscle in the body:

• Skeletal muscle - makes up the bulk of the body muscle tissue, these are the cells responsible for movement, they are striated with a regular arrangement so the muscle contracts in one direction, the contraction speed is rapid and the contraction length is short. Fibres are tubular and multinucleated.
• Caridac muscle - these muscle cells are only found in the heart. These cells are myogenic so they can contract without the need for a nervous stimulus, causing the heart to beat in a regular rhythm. They are specialised striated as the striations are much fainter than in skeletal muscles, they are controlled involuntarily, the cells branch and interconnect reuslting in simultaneous contraction, and have intermediate contraction speed and length, fibres are branched and uninucleated.
• Involuntary (smooth) muscle - these are muscle cells found in many parts of the body such as in the walls of hollow organs and in the walls of blood vessels. They are non striated and involuntarily controlled, they have no regular arrangement so cells can contract in different directions, they have a slow contraction speed but can remain contracted for a long time. they have no cross striations, fibres are spindle shaped and uninucleated.

Skeletal muscles are made up of bundles of muscle fibres which are envlosed within a plasma membrane known as a sarcolemma. The muscle fibres contain a number of nuclei and are much longer than normal cells, as they are formed as a result of many individual embryonic muscle cells fusing together, making the muscle stronger as points between adjacent cells would be points of weakness. The shared cytoplasm within a muscle fibre is known as sarcoplasm. Parts of the sarcolemma fold inwards (T tubules) to help spread electrical impulses throughout the sarcoplasm, ensuring that the whole of the fibre recieves the impulse to contract at the same time. Muscle fibres have lots of mitochondria to provide the ATP that is needed for muscle contraction. they also have a modified version of ER called sarcoplasmic reticulum which extends throughout the muscle fibre and contains the calcium ions required for muscle contraction.

Each muscle fibre contains many myofibrils which are long cylindrical organelles made of protein that are specialised for contraction. Myofibrils are made up of two types of protein filament:

• Actin - the thinner filament which consists of two strands twisted around each other.
• Myosin - the thicker filament which consists of long rod-shaped fibres with bulbous heads that project to one side.

Myofibrils have alternating light and dark bands resulting in their striped appearance:

• Light (I) bands - these appear light as they are the region where the actin and myosin filaments do not overlap.
• Dark (A) bands - these appear darl because of the presence of thick myosin filaments. the edges are particularily dark as the myosin is overlapped with actin.
• Z-line - this is a line at the centre of each light band, the distance between each Z-line is called a sarcomere, which is the dunctional unit of the myofibril, when the muscle contracts the sarcomere shortens.
• H-zone- this is a lighter coloured region found at the centre of each dark band, only myosin is present at this point. When the muscle contracts the H-zone decreases.

Slow twitch fibres are found in large proportions in muscles which help to maintain posture such as those in the back calf muscles which have to contract continuously to keep the body upright. The properties of slow twitch fibres include:

• Fibres contract slowly - provide less powerful contractions but over a longer period.
• Used for endurance activities as they do not tire easily.
• Gain their energy from aerobic respiration so are rich in myoglobin (bright red protein which stores oxygen), making the fibres appear red.
• Rich supply of blood vessels amd mitochondria.

Fast twtich fibres are found in high proportions in muscles which need short bursts of intense exercise, such as biceps and eyes. The properties of fast twitch fibres are:

• Fibres contract very quickly so produce powerful contractions but only for short periods.
• Used for shirt bursts of speed and power as they tire easily.
• Gain their energy from anaerobic respiration so are pale due to lower levels of myoglobin.
• Contain more and thicker myosin filamants and store creatine phosphate, which is a molecule which can rapidly generate ATP from ADP in anaerobiv conditions.

During contraction the myosin filaments pull the actin filaments inwards towards the centre of the sarcomere. The light band becomes narrower, the Z-lines move closer together, shortening the sarcomere, and the H-zone becomes narrower. The dark band remains the same width as the myosin filaments themselves don't shorten but overlap the actin filaments by a greater amount. The simultanous contraction of lots of sarcomeres means that the myofibrils contract, resulting in enough force to pull bone and cause movement. 

Myosin filaments have globular heads that are hinged which allows them to move back and forwards, on the head is a binding site for actin and ATP. Hundreds of aligned tails form the myosin filament.

Actin filaments have binding sites  myosin heads called actin-myosin binding sites. However these binding sites are often blocked by another protein called tropomyosin which is held in place by the protein troponin, so when the muscle is in a resting state the binding sites are blocked so contraction cannot occur. When a muscle is stimulated to contract the myosin heads form bonds with the actin filaments known as actin-myosin cross bridges, the mysoin heads then flex in unison pulling the actin filament along the myosin one. The myosin then detaches from the actin and its head returns to its normal angle using ATP, and then reattached further along the filament etc.

Muscle contraction is triggered when an action potential arrives at a neuromuscular junction - this is the point where a motor neurone and a skeletal muscle fibre meet. There are many of these junctions along the length of the muscle to ensure that all the all the muscle fibres contract simultaneously. All the muscle fibres are supplied by a single motor neurone known as a motor unit - the fibres act as a single unit, so if a strong force is needed, a larger number of motor units is stimulated and vice versa for a small force. when an action potential reaches the neuromuscular junction it stimulates calcium ion channels to open and calcium ions then diffuse from the synapse into the synpatic knob, where they cause synaptic vesicles to fuse with the presynatic membrane and ACT is released into the clef before binding to receptors on the sarcolemma resulting in depolarisation. ACT is then broken down into choline and ethanoic acid by ACTesterase and these components diffuse back into the neurone to reform ACT using the energy provided by mitochondria.

The depolarisation of the sarcolemma travels deep into the muscle fibre through the T tubules, which are in contact with the sarcoplasmic reticulum, which contains stored caclium ions which it actively absorbs from the sarcoplasm. When the action potential reaches the sarcoplasmic reticulum it stimulates calcium ion channels to open causing the calcium ions to diffuse rapidly down their concentration gradient flooding the sarcoplasm with calcium ions. The calcium ions bind to tropoin causing a change in its tertiary structure which means it pulls on the tropomyosin moving it awat from the actin-myosin binding sites on the actin filament. Now that the binding sites have been exposed the myosin heads bind to the actin filament forming an actin-myosin cross bridge. Once attached the myosin head flexes, pulling the actin filament along and the molecule of ADP bound to the myosin head is released. An ATP molecule can now bind to the head which causes the head to detach from the actin filament. The calcium ions present in the cyoplasm aslo activate the ATPase activity of the mysosin, hydrolysing ATP to ADP releasing energy which the myosin heads use to return to their orignal position. The myosin head can now attach itself to another actin-myosin binding site further along the actin filament and the cycle is repeated and the cycle continues for as long as the muscle is stimulated. During the period of stimulation many actin-myosin bridges form and break rapidly, pulling the actin filamet along, shortening the sarcomere and causing the muscle to contract.

Muscle contraction requires large quantities od energy which is provided by the hydrolysis of ATP into ADP and phosphate. The three main ways of generating ATP for use in the active absorption of calcium ions into the SR and the movement of the myosin heads are:

• Aerobic respiration: Most of the ATP used by muscle cells is regenerated from ADP during oxidative phosphory;ation which occurs inside the mitochondria which are plentiful in the muscle, but it can only occur in the presence of oxygen so aerobic respiration is used for long periods of low intensity exercise.
• Anaerobic respiration: In a very active muscle, oxygen is used up more quickly than the blood supply can replace it, therefore ATP has to be generated anaerobically via glycolysis, but as no oxygen is present the pyruvate which is also produced is converted into lactate which can quickly build up in the muscles causing muscle fatigue. Anaerobic respiration is used for short periods of high intensity exercise such as sprinting.
• Creatine phosphate: Another way the body can generate ATP is by using the chemical creatine phosphate which is stored in muscle and acts as a reserve supply of phosphate which is available to immediately combine with ADP reforming ATP. This system generates ATP rapidly but the store of phosphate is used up quickly, so it is used for short bursts of vigourous exercise. When the muscle relaxes the creatine phosphate is replenished.