NEURONES

NEURON CELL MEMBRANES ARE POLARISED AT REST - the outside is positively charged compared to the outside (more +ve ions outside than inside) SO THE MEMBRANE IS POLARISED - theres a difference in charge across it.

Resting potential is about -70MV. This is maintained and created by sodium - potassium pumps

• move NA+ ions out of the neurone - they cant difuse back in. CREATING A SODIUM ION ELECTROCHEMICAL GRADIENT
• Also move K+ ions in to the neurone - membrane is permeable to potassium ions so they diffuse back out through POTASSIUM ION CHANNELS
• This makes the outisde of the cell +ve compared to the inside. 

STIMULUS

• excites the neurone cell membrane causing NA+ channels to open.
• Na+ ions diffuse into the neurone down the sodium ion electrochemical gradient - making the inside of the neurone less negative.

DEPOLARISATION

• if the potential difference reaches the threshold (around -55mv) more sodium ion channels open - more sodium ions diffuse rapidly into the neurone.

REPOLARISATION

• at a potential difference of around +30mv the Na+ channels close & K+ channels open. 
• The membrane is more permeable to K+ ions so they diffuse out of the neurone down the potassium ion concentration gradient 
• This starts to get the membrane back to its resting potential. 

The action potential moves along the neurone as a wave of depolarisation.

• When an action potential occurs, some of the Na+ ions that enter the neurone diffuse sideways.
• Causing Na+ channels in the next region of the neurone to open & Na+ diffuse into that part.
• This causes a wave of depolarisation to travel along the neurone.
• The wave moves away from the parts of the membrane in the refractory period - these parts cant fire an action potential.

The refractory period produces discrete impulses 

• During the refractory period, ion channels are recovering and cant be opened
• So the refractory period acts a time delay between one action potential and the next
• This means that action potentials dont overlap, but pass along as discrete (seperate) impulses
• Also means theres a limit to the frequency at which the impulses can be transmitted.
• Also ensures that action potential are unidirectional.

Three factors affect the speed of conduction of action potentials.

MYELINATION

• Some neurones are myelinated - the myelin sheath is an electrical conductor
• In the peripheral nervous system, the sheath is made of a Schwann cell.
• Between the Schwann cells there are tiny patches of bare membrane - nodes of ranvier (Na+ channels are concentrated at the nodes)
• In a myelinated neurone, depolarisation only happens at the nodes of ranvier (where Na+ can get through the membrane)
• The neurones cytoplasm conducts enough electrical charge to depolarise the next node - the impulse 'jumps' from node to node.
• THIS IS SALTATORY CONDUCTION - its extremely rapid. 
• In a non - myelinated neurone, the impulse travels as a wave along the whole length of the axon membrane - this is slower than saltatory conduction. 

Synapse - junction between a neurone and the next cell.

• The pre-synaptic neurone has a synpatic knob - this contains synpatic vesicles filled with neurotransmitters
• When an action potential reaches the end of a neurone it causes neurotransmitters to be released into the synpatic cleft.
• They diffuse across the post-synaptic membrane and bind to specific receptors.
• This might trigger an action potential (in a neurone), cause muscle contraction ( in a muscle cell) or cause a hormone to be secreted (from a gland cell)
• As the receptors are on the post synaptic neurone - this keeps the synapse unidirectional.
• Neurotransmitters are removed from the cleft to prevent overstimulation - theyre broken down by enzymes.
• There are many different neurotransmitters - acetylcholine. Synapses that use acetylcholine are called cholinergic synapses. 

Neurotransmitters can be excitatory, inhibitory or both.

• Excitatory neurotransmitters depolarise the postsynaptic membrane, making it fire an action potential if the threshold is reached e.g. acetylcholine at the cholinergic synapses in the CNS
• Inhibiotry neurotransmitters hyperpolarise the postsynaptic membrane (making the p.d. more negative) preventing it from firing an action potential e.g. acetylcholine at cholinergic synapses in the heart.

Summation at synapses finely tunes the nervous response

If a stimulus is weak, only a small amount of neurotransmitter will be released from a neurone into the synaptic cleft, this might not be enough to excite the post synaptic membrane to the threshold level & stimulate an action potential.

Summation is where the effect of neurotransmitter released from many neurones is added together.

SPATIAL SUMMATION

• many neurones connect to one neurone
• the small amount released from each of these neurones altogether can reach the threshold in the postsynaptic neurone and trigger an action potential.
• If some neurones release an inhibitory neurotransmitter then the total effect may be no action potential.

TEMPORAL SUMMATION

• where two or more nerve impulses arrive in quick succession from the same presynaptic neurone.
• this makes an action potential more likely because more neurotransmitter is released into the synaptic cleft. 

Neuromuscular junction are synapse between neurones and muscles. These use the neurotransmiter acetylcholine which binds to nicotinic cholinergic receptors

Neuromuscluar junctions work in basically the same way as the cholingeric synapse but there are some differences:

• the postsynaptic membrane has lots of folds that form clefts - these secrete acetylcholinesterase that breaks down acetylcholine. 
• the postsynaptic membrane has more receptors than other synapses.
• acetylcholine is always excitatory at a neuromuscular junction, so when a motor neurone fires an action potential, it normally triggers a response in a muscle cell - this isnt always the case for a synapse between two neurones. 

Muscles act in antagonistic pairs

• Skeletal muscles are attached to bones by tendons.
• Ligaments attach bones to other bones
• Pairs of skeletal muscles contract and relax to move bones at a joint - antagonistic pairs.
• The contracting muscle is the agonist
• The relaxing muscle is the antagonist.

Muscles act as effectors and are stimulated to contract by neurones

• Skeletal muscle is made up of large bundles of muscle fibres
• The cell membrane of muscle fibres is the sacrolemma
• Bits of the sarcolemma fold inwards across the muscle fibre and stick into the sarcoplasm - these are t-tubules.
• T-tubules help spread electrical impulses throughout the sarcoplasm.
• A network of internal membranes (sarcoplasmic reticulum) runs through the sarcoplasm. The SR stores and releases calcium  ions for muscle contraction.
• Muscle fibres are multinucleate (multiple nuclei)
• Muscle fibres have long, cylindircal organelles (myofibrils) . these are made up of actin & myosin (proteins highly specialised for muscle contraction.

Myofibrils contain thick myosin filaments and thin action filaments.

Under an electron microscope,

• dark bands contain thick myosin filaments & some overlapping thick actin filamnets - these are A-bands
• light bands contain thin actin filamnets only - these are I - bands.

A myofibril is made up of many short sarcomeres, the end of a sarcomere is marked with a z-line. In the middle of each sarcomere is an M-line - middle of myosin filaments. Around the M-line is the H-zone - these contain myosin filamnets only.

Muscle contraction is explained by the sliding filament theory.

• Myosin and actin filaments slide over one another to make the sarcoemeres contract - myofilaments dont contract.
• The simultaneous contraction of lots of sarcomeres means the myofibrils and muscle fibres contract
• Sarcoemeres return to their original length as the muscle relaxes.

Myosin filaments have golbular heads, these are hinged and binding sites for actin and a seperate binding site for ATP

Actin filaments have binding sites for myosin heads - these are actin - myosin binding sites.

Tropomyosin is found between actin filaments - helps myofilaments move past each other.

In a resting muscle the actin-myosin binding site is blocked by tropomyosin - myosin heads cant bind so myofilaments cant slide past each other.

ATP and Phosphocreatine provide the energy for muscle contraction, these are genereated in three ways.

• Aerobic respiration
• Anaerobic respiration
• ATP-Phosphocreatine (PCr) system - ATP is phosphorylated by the P from PCr.
• PCr is stored inside cells and the ATP-PCr system generates new ATP very quickly
• PCr runs out after a short time so is used in short burts of vigorous execrise
• The ATP-PCr system is anaerobic and alactic
• Cr gets broken down into creatinine and removed by the kidneys.
• High creatinine levels can be seen in people who exercise reg, and those with a high muscle mass. They may also indicate kidney damage.

• When an action potential stimulates a muscle cell, it depolarises the sarcolemma - this depolarisation spreads down the T-tubules into the sarcoplasmic reticulum.
• The SR then releases stored Ca2+ into the sarcoplasm
• Ca2+ bind to a protein attached to tropomyosin - causing the protein to change shape, this pulls the attached tropomyosin out of the actin-myosin binding site on the actin filament.
• This exposes the binding site, allowing the moysin head to bind, forming an actin - moysin cross bridge
• Ca2+ also activate ATP hydorlase which hydrolyses ATP to provide the energy needed for the moysin head to bend, pulling the actin filament along ( a rowing action)
• Another ATP molecule provides the energy to break the actin-myosin cross bridge
• The myosin head then attaches to a different binding site further along the actin filament, a new cross bridge is formed and the cycle is repeated.
• Many cross bridges form and break rapidly, pulling the actin filament along - shortening the sarcomere and causing muscle contraction
• The cycle will continue as long as Ca2+ are present.
• When the muscle stops beinh stimulated, Ca2+ leave their binding sites and are actively transported back into the sarcoplasmic reticulum.
• This causes the tropomyosin molecules to move back so they block the actin-moysin binding sites again.
• No myosin heads are attached to actin filaments - no muscle contraction, the actin filaments slide back to their relaxed position - lengthening the sarcomere.

Skeletal muscles are made up of slow twitch muscle fibres and fast twitch muslce fibres

SLOW TWITCH

• contract slowly
• muscles you use for posture have a high proportion of slow twitch
• good for endurance activities
• can work for a long time without getting tired
• energy's released slowly through aerobic respiration - lots of mitochondria and blood vessels supply the muscles with O2
• red in colour - rich in myoglobin (red colour protein that stores oxygen)

FAST TWITCH

• contract very quickly
• muscles used for fast movement have lots of fast twitch e.g. eyes and legs
• god for short bursts of speed and power
• get tired very quickly
• energy's released quickly through anaerobic respirationusing glycogen - few mitochondria or blood vessels
• whitish in colour because they dont have much myoglobin

HYPERPOLARISATION

• Potassium ion channels are slow to close so theres an 'overshoot' where too many K+ diffuse out of the neurone. 
• P.d becomes more negative than the resting potential (<-70mv)

RESTING POTENTIAL

• Ion channels are reset 
• Sodium - potassium pump returns the membrane to its resting potential and maintains it until the membranes excited by another stimulus.

REFRACTORY PERIOD

• After an action potential, the  neurone cell membrane cant be excited again straight away - because the ion channels
• are recovering & cant be made to open - Na+ channels are close during repolarisation & K+ channels are closed during hyperpolarisation.
• This period of recovery is called the refracotry period.

AXON DIAMETER

• Axons with bigger diameters conduct action potentials quicker because theres less resistance to the flow of ions.
• With less resistance, depolarisation reaches other parts of the neurone cell membrane quicker.

TEMPERATURE

• Speed of conduction increases as the temp increases because ions diffuse faster.
• Around 40c the proteins begin to denature and the speed decreases. 

Some drugs affect the action of neurotransmitters at synapses in various ways

• some are the same shape as neurotransmittersso they mimic their action at receptors - AGONISTS. More receptors are activated. e.g. nicotine mimics acetylcholine so binds to nicotinic cholinergic receptors in the brain.
• Some block receptors so they cant be activated by neurotransmitters - ANTAGONISTS. Means fewer receptors are activated. e.g curare blocks the effects of acetylcholine by blocking nicotinic cholinergic receptors at neuromuscular junctions - muscle cells arent stimulated, muscle is paralysed.
• Some inhibit the enzyme that breaks down neurotranmitters - means there are more neurotransmittersin the synaptic cleft to bind to receptors. e.g. nerve gases stop acetylcholine from being broken down in the synaptic cleft - can lead to loss of muscle control.
• Some stimulate the release of neurotransmitters from the presynaptic neurone so more recpetors are activated e.g. amphetamines.
• Some inhibit the release of neurotransmitters from the presynaptic neurone so fewer receptors are activated e.g alcohol.

Action potentials have an all-or-nothing nature 

• Once the threshold is reached, an action potential will always fire with the same change in voltage
• If the threshold isnt reached, an action potential wont fire - all or nothing.
• A bigger stimulus wont cause a bigger action potential, but cause them to fire more frequently.