NERVOUS COORDINATION AND MUSCLES As species have evolved, their cells have become adapted to perform specialist functions. By specialising in one function, they lost the ability to perform other functions. This therefore made cells dependent upon other cells to carry out functions they no longer specialise in. these different functional systems must be coordinated if they to perform the function efficiently, therefore must be coordinated. There are two main forms of coordination in animals – nervous and hormonal:

- Nervous system uses nerve cells to pass electrical impulses along their length. They stimulate target cells by secreting/producing chemicals – neurotransmitters – directly on to them. Results in rapid communication between parts of an organism. The responses are usually short-lived and restricted to a local region of the body.

- Hormonal system produced hormones that are transported in blood plasma to target cells. These target cells have specific receptors in their cell-surface membranes and the change in the concentration of hormones stimulates them. This is slower, less specific form of communication between parts of an organism; response is long-lasting and widespread.

Neurones – nerve cells – specialised cells adapted to rapidly carry electrochemical changes, nerve impulses from one part of the body to another. A mammalian motor neurone is made up of:

- Cell body – contains organelles, including nucleus and large amount of RER, which associated with production of proteins and neurotransmitters.

- Dendrons – extensions of the cell body which subdivided into small branched fibres, dendrites, that carry nerve impulses towards the cell body

- Axon – a single long fibre that carries nerve impulses away from the cell body - Schwann cells – surround the axon, protecting it and providing electrical insulation. They

carry out phagocytosis (removal of cell debris) and play a part in nerve regeneration. They can wrap around the axon many times, so that layer of their membranes build up around it

- Myelin sheath – forms a covering to the axon and is made up of the membranes of Schwann cells. The membranes are rich in lipid, myelin. Neurones with myelin sheath are called myelinated neurones

- Nodes of Ranvier – constrictions between adjacent Schwann cells where there is no myelin sheath

Neurones can be classified according to their function:

- Sensory neurones – transmit nerve impulses from a receptor to an intermediate or motor neurone. Have one Dendron that is often very long, which carries the impulse towards the cell body. Has one axon that carries it away from the cell body.

- Motor neurone – transmits nerve impulse from an intermediate or relay neurone to an effector. Have a long axon and many short dendrites.

- Intermediate or relay neurone – transmit impulses between neurones, have numerous short processes

Nerve impulse – self-propagating wave of electrical activity that travels along the axon membrane; a temporary reversal of potential difference across the axon membrane. The potential difference is between resting potential and action potential. Resting potential The movement of ions, like sodium ions and potassium ions, across the axon membrane is controlled by:

- The phospholipid bilayer of the axon plasma membrane prevents sodium and potassium ions diffusing across it

- Channel proteins spanning the bilayer have ion channels, which pass through them. Some of these channels have gates, which can be opened or closed, so sometimes the ions can move through them by facilitated diffusion and other times cannot. Sodium and potassium have different channels. Some channels remain open all the time, so the ions move through them by facilitated diffusion unhindered.

- Some carrier proteins, sodium-potassium pump (intrinsic) actively transport potassium ions into the axon and sodium out of the axon.

Resting potential ranges from 50 to 90 millivolts (mV), usually 65mV in humans. It is maintained by active transport. Axon is said to be polarised. Process of establishing resting potential:

- Sodium ions are actively transported out of the axon by sodium-potassium pumps. - Potassium ions are actively transported into of the axon by sodium-potassium pumps. - Active transport of sodium ions is greater than that of potassium ions, so 3 sodium ions are

moved out while 2 potassium ions are moved in. - Because the outward movement of sodium is greater than that of inward movement of

potassium, there is an electrochemical gradient created. Sodium – more in tissue fluid surrounding the axon then in cytoplasm; potassium the opposite.

- Sodium ions begin to diffuse back naturally into the axon while potassium out. But gates of potassium ion are open, while gates of sodium ions are closed.

Active potential When a stimulus of sufficient size is detected by a receptor in the nervous system, its energy causes a temporary reversal of the charges either side of the axon membrane. If the stimulus I great enough, then the negative charge of -65mV inside the membrane becomes positive charge of around +40mV. This is action potential and axon membrane is called depolarised. Depolarisation occurs because channels change shape and so open or close, depending on the voltage across the membrane. They are called voltage-gated channels. Process:

- At resting potential potassium voltage-fated channels are open (mostly those that are permanently open) but sodium voltage gated channels are closed.

- Energy of the stimulus causes some sodium voltage-gated channels to open and so sodium ions diffusion into the axon long the electrochemical gradient. Because they are positively charged, they trigger a reversal in potential difference across the membrane.

- The more sodium ions diffuse, the more sodium channels open, causing a greater influx of sodium ions diffusion.

- Once the action potential of around +40mV has been established, the voltage gates on sodium ion channels close and voltage gates on potassium ion channels open.

- With potassium voltage-gated channels open, the electrical gradient that was preventing potassium ions to move out is reversed, causing more potassium ion channels to open. They diffuse out, starting repolarization of axon. This outward diffusion of potassium ions case a temporary overshoot of electrical gradient – hyperpolarization – inside more negative than usual. Closable gates of potassium ion channels close. The normal activity resumes. The resting potential of -65mV is re-established, axon is called repolarised.

Action potential involved diffusion – passive process, while resting potential involves active transport, active process. Action potential – axon membrane transmitting a nerve impulse. Resting potential – transmitting no nerve impulse.

Passage of an action potential An action potential, once created, moved rapidly along an axon. The size of action potentials remains the same at each point. Depolarisation of one region of axon stimulates depolarisation of the next region of axon. So action potential is a travelling wave of depolarisation. The previous region of the membrane returns to its resting potential i.e. undergoes repolarisation. To understand how a nerve impulse is propagated in a myelinated neurone, first is needed to understand how it is propagated in an unmyelinated one.

In myelinated axons, the fatty sheath of myelin around the axon acts as an electrical insulator, prevention action potentials from forming. At intervals of 1-3mm there are breaks in myelin insulation – nodes of Ranvier, at which action potential can occur. Localised circuits are created bewteen adkacent nodes of Ranvier. Action potentials in effect jump from node to node in a process known as saltatory conduction. So across the myuelinated axon the action potential travels faster than along an unmyelinated axon. In out Maxican wave analogy, this is equivanent to a whole black os spectators leaping up simultanously, followed by the next block.

Once an action potential has been set up, it movies rapidly from one end of the axon to the other without any decrease in size. Nerve impulse – the transmission of action potential along the axon The action potentials may travel at speed of 0.5 o 120 m/s. The factors effecting the speed include:

- Myelin sheath – allows faster movement by saltatory conduction, whives inreased speed from 30 m/s in an unmyelinated neurone to 90m/s/ in a similar myelinated neurone.

- Diameter of axon – the greater the diameter of axon, the faster the speed of conductance. This is due to less leakage of ions from a large axon (leakage makes membrane potentials hader to maintain).

- Temperature – effects rate of dissuion of ions ad so fater nerve impulse. The energy for active transport comes from respiration, respiartion and sodium-potassium pump are controleed by enzymes, enzymes function faster at higher temperatures but up to a point. Above a certain temperature enzumes and plasma membrane porteins denature and so impulse fails.

Temperature is therefore an important factor in response times in cold-blooded (ectrothermic) animals and would effect speed and strength of muscle contractions. Nerve impulses are described as all-or-nothing responses. There is a certain level os stimulus, threshold value, that triggers an action potential. If the stimulus is below, no action poential and so impulse is generated. Any stimulus above threshold value will succeed in generatuon action potential, and so impilse. Action potential are all relatively the same size, so though the size of action potential the size of stimulus cannot be detected. It is detected by: - Number of impulses passing in a given time, the larger the stimulus the more impulses are

generated in given time - Having different nurones with different threshold values. Brain interprets the number of

neurones that pass impulses and so determines its size Once an action potential has been created in any region of an axon, there is a period afterwards when inward movement of sodium ions is prevented because the sodium voltage-gated channels are closed. During this it is impossible for a furcther action potential to be generated. This period is known as refractory period. The refractor period serbed three purposes:

- Ensures that action potentials are propagated in one direction only. Action potentials can only pass from an active region to resting region. Action potentials cannot propagated in a region that is refractory (resistant to process or stimulus), so can only move in forward direction. This prevents action potentials from spreading out in both directions.

- Produces descirete impulses – due to refractory period a new action potential cannot be formed immediately behind the first one. This ensures that action poentials are spearated from one another.

- Limits the number of action potentials – as action potentials are separated from one another this minits the number of action potentials that can pass along an axon In a given time, so limits the strength of stimulus can be detected.

Structure and function of synapses Synapse – a point where one neurone communicates with another or with an effector. They are important in linking different neurones together and so coordinating activities. Structure of a synapse Synapses transmit information, not impulses, from one neurone to another by means of chemicals, neurotransmitters. Neurones are separated by a small gap, synaptic cleft which is 20-30nm wide. Presynaptic neurone – the neurone that released the neurotransmitter

Synaptic knob – swollen portion of the end of axon neurone. It possess many mitochondria and large amounts of endoplasmic reticulum, which are need to manufacture neurotransmitters. Synaptic vesicles – where neurotransmitters are stored After the neurotransmitter is released from the vesicles it diffuses across to the postsynaptic neurone, which possesses specific receptor proteins on its membrane to receive it. Features of synapses Unidirectionality – they can only pass information in one direction, from the presynaptic neurone to the postsynaptic neurone. In some way, synapses act like valves. Low frequency action potentials often lead to release of insufficient concentrations of neurotransmitter to trigger a new action potential in the postsynaptic neurone. But they can in summation, which is a rapid build-up of neurotransmitter in the synapse by two methods.

- Spatial summation – number of different presynaptic neurones together to release enough neurotransmitters to exceed the threshold value, so trigger new action potential.

- Temporal summation – a single presynaptic neurone releases neurotransmitter many times over a very short period. If the concentration of neurotransmitter exceeds the threshold value, then new action potential is triggered.

Some synapses make it less likely for new action potential to happen, inhibitory synapses.

- The presynaptic neurone releases a type of neurotransmitter that binds to chloride ion protein channels on the postsynaptic neurone.

- Neurotransmitter causes the chloride ion protein channel to open. - Chloride ions (Cl-) move into the postsynaptic neurone by facilitated diffusion. - The binding of neurotransmitter causes the opening of nearby potassium (K+) protein

channels, which move out of the postsynaptic neurone into synapse. - This causes overall postsynaptic membrane more negative and the outside more positive. - The membrane potential increases to up to -80mV compare to usual -65mV at resting

potential. - This is called hyperpolarisation and makes it less likely that a new action potential will be

created, because a large influx of NA+ needed to produce one. Function of synapses: Synapses transmit information from one neurone to another. So they act like junction, allowing:

- A single impulse along one neurone to initiate new impulses in a number of different neurones at a synapse. This allows a single stimulus to create simultaneous responses.

- A number of impulses to be combines at a synapse. This allows nerve impulse from receptors reacting to different stimuli to contribute to a single response.

A neurotransmitter is made only in the presynaptic neurone and not in the postsynaptic neurone. The neurotransmitter is stored in synaptic vesicles. When an action potential reaches the synaptic knob, the membranes of these vesicles fuse with the pre-syntactic membrane to release neurotransmitter. When released, neurotransmitter diffuses across the synaptic cleft to bind to specific receptor proteins which are found only on the postsynaptic neurone. Neurotransmitters bind with receptor proteins, which lead to action potential in postsynaptic neurone. Synapses that produce new action potentials in this way are called excitatory synapses.

Transmission across a synapse Cholinergic synapse – the one which produces neurotransmitter acetylcholine. They are common in vertebrates, occur in central nervous system and neuromuscular junctions (junctions between neurones and muscles). Acetylcholine – made up of two parts, acetyl (ethanoic acid) and choline. Effects of drugs on synapses Excicatory – neurotransmitters and receptors that leads to a new action poential in the postsynaptic neurone. Inhibitatory – neurotransmitters and receptors that makes it less likely that a new action potential will be created in postsynaptic neurone. There are many diferent types of receptors on the postsynaptic neurone, each is complementary to a specific neurontransmitter due to their shape. The action of a specific neurontrasmitter depends on the sepcific receptor to which it binds to. As our perception of the world is through stimuli detected by recpetros and information transmferred to the brain as nerve impulses by neurones that connect via synapses, it is not surpringing that many medical and rectionatinal durgs effect sunapses. Drugs act on synapses in two main ways:

- Stimulate nervous system by creating more action potentials. A drug could mimic the neurotransmitter, stimulating the more release of it or inhibiting enzume that breaks down the neurotransmitter. The outcome is to enchance the body’s responses to impulses/stimuli.

- Inhibit the nervous system by creating fewer action potentials. A drug might inhibit the release on neurortansmitter or block the sodium/potassium ion channels. The outcome is to reduce the impulses/effect of stimuli.

A dug may inhibt the action of excitatory neurortansmitter reducing the effect, or inibit an inhibitory neurortansmitter which will enchance the effect. Exampels of some drugs and their effect on synapses

Drug Effect How/Why?

Pain reducing drugs, like morphine and codeine

Block sensation of pain Bing to receptors in brain used by endorphins (neurortansmitters used by pain pathways).

Prozac Regulaties sleep and certain emotional states.

Effects serotonin within synaptic clefts (serotonin is a neurotransmitter invovled in regulation of sleep and cetrain emotional states. Its decrease is through to be one of the causes of clinical depression.)

Valium Enchanes the bdinging of GABA to its receptors (GABA is a neurotransmitter that inhibits the formation of action poetntials when it binds to postsynapticn neurones).

Nicotine and Caffeine Facilitations/ alertnessby lowering the threshold for activation/generating action potential.

It mimcs the action of acetylcholine.

Atropine Inhibits parasympathetic functions

Blocks action of acteylchonine in parasympathetic sunapses

Curare Paralysis, muscles not able to be stimulated

Blocks the niotinic cholinergic receptors at neuromuscular juctions, preventing acteylcholine binding to it and so not stimulating the muscle

Nerve gases Loss of muscle control, over stimulation

Prevents actylchloine to be broke down in the synaptic cleft by inhibiting the enzyme

Amphetamines

Opioids

Curare blocks the action of acetylcholine at the neuromuscular junctions and thus causes paralysis.

Structure of skeletal muscle Muscles are effectors organs that respond to nervous stimulation contraction, so creating movement. There are three types of muscles in the body:

- Cardiac muscle – found exclusively in the heart, acts under unconscious control. - Smooth muscle – found in the walls of blood vessels and gut, acts under unconscious control - Skeletal muscle – attached to bone and acts under voluntary control.

Individual muscles are made up of millions of tiny muscles fibres, myofibrils. On their own they produce almost no force but collectively they can be very powerful. They are lined up parallel to each to maximum force. Smaller muscles are bundled into progressively larger ones.

Separate cells have become fused together unto muscle fibres, which share nuclei and cytoplasm, (sarcoplasm) that is mostly found in the circumference of the fibre. Sarcoplasm is large concentration of mitochondria and endoplasmic reticulum. Myofibrils are made up of two types of protein filament:

- Actin, which is thinner and consists of two strands twisted around one another. - Myosin – thicker and consist of long rod-shaped tails with bulbous heads that project on the

side. Myofibrils appear stripped due to their alternating light-coloured, I bands (isotropic bands) and dark coloured bands, A bands (anisotropic bands). I bands appear lighter because the thick and thin filaments do not overlap in that region. A bands appear darker because they do overlap in that region. H-zone - a lighter-coloured region at centre of each A band. Z-line – a line at the centre of each I band. Sarcomere – distance between adjacent Z-lines. When a muscle contracts the sarcomeres shorten and the patter of light and dark bands changes. The arrangement of sarcomeres into a long line means that, when one sarcomere contracts a little, the line as whole contracts a lot. Having the lines of sarcomeres running parallel to each other means that all the force is generated in one direction. Tropomyosin – another important protein found in muscle, which forms a fibrous strand around the actin filament. Types of muscle fibre

- Slow-twitch fibre – contract more slowly and provide less powerful contractions but over a longer period. They are adapted to endurance work. They are suited to this role by being adapted for aerobic respiration in order to avoid build-up of lactic acid, making fibres less effective and prevent long-duration contraction. Adaptations include:

Large store of myoglobin (molecule that stores oxygen)

Rich supply of blood vessels to deliver oxygen and glucose for aerobic respiration

Numerous mitochondria to produce ATP - Fast-twitch fibres – contract more rapidly and produce powerful contraction but only for a

short period. Adapted to intense exercise. Adaptations for their role include:

Thicker and more numerous myosin filaments

Higher concentration of glycogen

Higher concentration of enzymes involved in anaerobic respiration (provides ATP quicker)

Store of phosphocreatine, molecule that can rapidly generate ATP from ADP in anaerobic conditions.

Neuromuscular junction – the point where a motor neurone meets a skeletal muscle fibre. There are many neuromuscular junctions spread throughout the muscle to have rapid, coordinated and powerful muscle contraction, essential for survival. All muscle fibres supplied by a single motor neurone act together as a single functional unit, known as motor unit. This controls the amount of force – only a few units a stimulated for a slight force and larger number of units are stimulated for a greater force.

When a nerve impulse is received at the neuromuscular junction, the synaptic vesicles fuse with the presynaptic membrane and release acetylcholine. Acetylcholine diffuses to postsynaptic membrane, altering its permeability to sodium ions, which enter quickly and depolarises the membrane. Acetylcholine is broken down by acetylcholinesterase into choline and ethanoic acid (acetyl) to ensure that the muscle is not over-stimulated. The products diffuse back into the neurone where they are recombined to form acetylcholine using energy provided by mitochondria. Similarities between neuromuscular junction and cholinergic synapse

- Have neurotransmitters that are transported by diffusion - Have receptors that cause influx of sodium ions - Use sodium-potassium pump to repolarise the axon - Use enzymes to breakdown the neurotransmitter

Neuromuscular junction Cholinergic synapse

Only excitatory May be excitatory or inhibitory

Only links neurones to muscles Links neurones to neurones, or neurones to other effector organs

Only motor neurones are involved Motor, sensory and intermediate neurones may be involved

The action potential ends here (end of neural pathway)

A new action potential may be produced along another neurone (postsynaptic neurone)

Acetylcholine binds to receptors on membrane of muscle fibre

Acetylcholine binds to receptors on membrane of post-synaptic neurone

Contraction of skeletal muscle As muscles are attached to the skeletan, if a muscle externs a force, via tendonws the bone moves. The parts of skeleton can be moved relative to one another around a series of points called joints. Muscles can only pull not push. Therefore each muscle can only move in one particular direction only. To move the limb in the opposite direction requires a second muscle that works antagonistically to the first one. In doing so it streaches its partner muscle (which has relaxed0 returning it to its original state ready to conrtact again. Therefore skeletal muscles occur and act in antagonistic pairs. Sliding filament mechanism – the contraction process of a muscle fibre, called that because it involves actin and myosin filaments sliding past one another. Evidence for the sliding filament mechanism: If the sliding filament is correct, then there will be more overlap of action and myosin in a contracted muscle then in a relzed one. When the muscle conrtacts the following are absorbed:

- I bands become narrower - Z lines move closer together/sarcomere shortens - H zone becomes narrower - A band remain the same with

As A band remains the same and its width depends on the length of myosin filaments, it can be conlcluded that filaments themsves to do not decrease in length, discouraging this theory. So overlapping must tehrefore occur. Three main porteins involved in the sliding filament mechanism:

- Myosin – made up of two types of protein

Fibrous protein arranged into a filement made of several hundred molecules (the tail)

Globular protein formed into two bulbous structrue at one end (head) - Actin – globular portein whose molecules are arranged into long chains twisted around each

other to form a helical strand. - Tropomyosin – forms long thin threads that are wound around actin filaments.

The process of sliding filament mechanism of muscle conrtaction is continuous but was divided into groups for easier understanding. Muscle stimulation:

- Action potential reaches many neuromuscular junctions simultanously, causing calcium ion protein channels to open and calcium ions to diffuse into synaptic knob.

- The presence of calcium ions cause the synaptic vesicles to fuse with the presynaptic membrane and release acetylcholine into synaptic cleft.

- Acetylcholine diffuses across the synaptic cleft and binds with receptors on a muscle cell-surface membrane, causing it to be depolarised.

Muscle contraction: - Action potential travels into the fibre through a sustem of tubules (T-tubules) that are

extension of cell-surface memrbane and branch through the sarcoplasm (muscle’s sytoplasm).

- The tubules are in contact with the sarcoplasmic reticulum (ER of muscle). They actively transport calcium ions from sarcoplasm, creating a concentration gradient.

- Action potential opens calcium ion voltage-gated protein channels on ER and calcium ions diffuse into sarcoplasm down a concentration gradient.

- Calcium ions cause tropomyosin molucules blocking the binding sites of actin filament to pull away/expose it.

- ADP attach to myosin heads allowing them to bind to actin filament and form a cross-bridge. - When they do attach, myosin heads change their angle and pull the actin flimaent along,

releasing ADP molecule in the process. - ATP molecule attaches to each myosin head, causing it detatch from actin filament. - The calcium ions the activate ATPase, which hydrolyses ATP to ADP and Pi. The hydrolysis

provides energy for myosin head to return to its original position. - Myosin head is reatached with ADP molecule and reattached itself further along the actin

filament. - The cycle is repeated as long as the concenrtation of calcium ions remains high. - As myosin molecules are joined tail to tail in two opesitely facing sets, the movement of one

set is in the opposite direaction to the other set. - The movement of actin filaments in opposing drieactions pulls them twoards each other,

shortening the distance between the lines. Muscle relaxation

- When revous stimulation ceases, calcium ions are actively transported back into ER usuing energy from hydrolysis of ATP.

- Reabsorbtion of calcium ions allos tropomyosin to block the actin filament. - Myosin heads are now unable to bind to actin filaments, contraction ceases, muscles

relaxes. - Force from antagonistic muscles can pull actin filaments out form between myosin to a

point. Summary of the mechanism:

Bulbous heads of myosin filaments form cross-bridges with the actin filaments, then flex in unison which causes the actin filaments to be pulled along the muosin filaments. Then they become detached, and using ATP as a source of energy, return to the original angle and re-attach themselves furtehr along the actin filament. Muscle contraction requires energy, which is supplied by hydrolysis of ATP. It ised for movement of musoin heads and reobsorbtion of calcium ions. ATP is regenerated using mitochondria but if there is lack of oxygen, to improve production of ATP using anaerobic respiration is chemical phosphocreatine and more glycolysis. Phosphocreatine regenerates ATP. It is stored in the muscle and acts as a reserve supply of phosphate. The store is replenished when muscle is relaxed.

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