Nerves and Muscles

Neurone cell membranes are polarised at rest.

• Outside is positively charged compared to the inside
• Resting potential is around -70mV
• It is created and maintained by sodium-potassium pumps which use active transport to move 3 Na+ out of the neurone for every 2 K+ that move in

When stimulated, neurone cell membranes become depolarised- the difference in charge between the outside and inside decreases, so the potential difference becomes less negative. This is because a stimulus excites the neurone cell membrane, causing Na+ channels to open, and if the stimulus is large enough it will trigger a rapid change in potential difference due to many more Na+ channels opening as threshold potential is reached.

All-or-Nothing Nature:

• Once the threshold is reached, an action potential will always fire with the same potential difference, and if the threshold isn't reached an action potenial won't fire
• A bigger stimulus causes more frequent action potentials- it has no impact on AP size

Movement of Action Potential:

• Some Na+ diffuses sideways along the neurone, causing Na+ in the next region of the neurone to open and Na+ to diffuse into that area
• A wave of depolarisation travels along the neurone
• The wave moves away from parts of the membrane in the refractory period as these parts can't fire an action potential

Refractory Period:

• During this time the ion channels are recovering and can't be opened
• It acts as a time delay between two action potentials, ensuring that:
  1) They don't overlap and travel as discrete impulses
  2) They are unidirectional (travel in one direction)
  3) There is a limit to the frequency at which nerve impulses can be transmitted

The speed of conduction of action potentials is affected by:
1) Myelination:

• Some neurones have a myelin sheath, an electrical insulator, made up of Schwann cells
• Between each Schwann cell are patches of bare membrane called nodes of Ranvier, where there are many Na+ channels
• Depolarisation only occurs at nodes of Ranvier, as the cytoplasm conducts enough electrical charge. This is really fast and is called saltatory conduction
• In a non-myelinated neurone, depolarisation occurs over the whole length of the axon membrane, which is slower than conduction in a myelinated neurone

2) Axon diameter:

• Action potentials are conducted quicker along axons with larger diameters as there is less resistance to the flow of ions so depolarisation of the length of the neurone membrane is faster

3) Temperature:

• As temperature increases (up to 40 degrees), conduction speed increases as the ions diffuse faster

• A synapse is the junction between two neurones, or a neurone and an effector cell
• The gap between the cells at the synapse is called the synaptic cleft
• The presynaptic neurone has a swelling containing synaptic vesicles filled with neurotransmitters- this swelling is called a synaptic knob
• When an action potential reaches the end of a neurone it causes neurotransmitters to be released into the synaptic cleft
• The postsynaptic membrane contains specific receptors, which the neurotransmitter binds to after diffusing across the synaptic cleft. This could trigger an action potential, cause a hormone to be secreted, or muscle contraction.
• Neurotransmitters are removed from the synaptic cleft, by either being taken back into the presynaptic neurone or being broken down by enzymes, so the response doesn't keep happening.
• Synapses ensure impulses are unidirectional because:
  1) Vesicles containing neurotransmitters are only found in the presynaptic neurone
  2) Receptors are only found on the postsynaptic membrane

There are 3 types of neurotransmitter- excitatory, inhibitory, or both:
1) Excitatory- These depolarise the postsynaptic membrane, making it fire an action potential if the threshold is reached. E.g. acetylcholine is excitatory at cholinergic synapses in the CNS- it binds to receptors to cause an action potential at neuromuscular junctions and in the postsynaptic membrane
2) Inhibitory- These hyperpolarise the postsynaptic membrane, making the potential difference more negative, preventing it from firing an action potential. E.g. acetylcholine is inhibitory in the heart- when it binds to receptors, it causes K+ channels to open, hyperpolarising the postsynaptic membrane

Summation at synapses enables fine tuning of nervous responses. There are two types:
1) Spatial summation
- Sometimes many neurones connect to one neurone
- The small amount of neurotransmitter released from each of these neurones can be enough altogether to reach the threshold in the postsynaptic neurone and trigger an action potential, but if some neurones release inhibitory neurotransmitters this may result in no action potential

2) Temporal summation
- When two or more impulses arrive in quick succession from the same presynaptic neurone
- An action potential is more likely as more neurotransmitter is released into the synaptic cleft

- In a cholinergic synapse, the neurotransmitter is acetylcholine (ACh)

1) An action potential arrives at the synaptic knob of the presynaptic neurone, which stimulates voltage-gated calcium ion channels to open
2) Calcium ions diffuse into the synaptic knob, causing the synaptic vesicles to move to and fuse with the presynaptic membrane
3) The vesicles release the neurotransmitter, ACh, into the synaptic cleft. This is called exocytosis
4) ACh diffuses across the synaptic cleft and binds to specific cholinergic receptors on the postsynaptic membrane and Na+ channels open so Na+ diffuses into the postsynaptic membrane
5) The influx of Na+ causes depolarisation and an action potential is produced if the threshold is reached
6) ACh is removed from the synaptic cleft to prevent the response from happening again. It is broken down by the enzyme acetylcholinesterase and the products are re-absorbed by the presynaptic neurone so they can be used to synthesise more ACh

Effects of drugs on synaptic transmission:

• Some drugs are the same shape as neurotransmitters so they mimic their action at receptors, meaning more receptors are activated. These drugs are called agonists.
• Some drugs block receptors so they can't be activated by neurotransmitters, meaning fewer receptors can be activated. These drugs are called antagonists.
• Some drugs inhibit the enzyme that breaks down neurotransmitters, so there are are more neurotransmitters in the synaptic cleft to bind to receptors and they're there for longer.
• Some drugs stimulate the release of neurotransmitters from the presynaptic neurone so more receptors are activated, e.g.amphetamines
• Some drugs inhibit the release of neurotransmitters from the presynaptic neurone so fewer receptors are activated, e.g. alcohol

Skeletal muscle is the type of muscle that is used in movement. It works in antagonistic pairs in which the contracting muscle is the agonist and the relaxing muscle is the antagonist.

• The muscle is made up of muscle fibres, and the cell membrane of muscle fibre cells is called the sarcolemma. Bits of the sarcolemma fold inwards and stick into the sarcoplasm (the cell's cytoplasm). These are called transverse (T) tubules and help spread electrical impulses throughout the sarcoplasm so they reach all parts of the muscle fibre. The sarcoplasmic reticulum, a network of internal membranes that stores and releases calcium ions, runs through the sarcoplasm. Muscle fibres are also multinucleate (have many nuclei) and contain lots of mitochondria. They also have lots of myofibrils which are made up of proteins and are specialised for contraction.

1) When an action potential from a motor neurone stimulates a muscle cell, it depolarises the sarcolemma, which spreads down the T-tubules to the sarcoplasmic reticulum.
2) The sarcoplasmic reticulum releases calcium ions into the sarcoplasm. They attach to a protein attached to tropomyosin, causing the protein to change shape.
3) This pulls tropomyosin out of the actin-myosin binding site, exposing the binding site which allows the myosin head to bind, forming an actin-myosin cross bridge.
4) Calcium ions also activate ATP hydrolase which hydrolyses ATP to provide the energy needed for muscle contraction.
5) The energy released causes the myosin head to bend, sliding the actin filament along.
6) Another ATP molecule is used to break the actin-myosin cross bridge, so the myosin head detaches from the actin filament after it has moved.
7) The myosin head reattaches to a different binding site further along the actin filament, so a new actin-myosin cross bridge is formed and the cycle repeats itself. Many cross bridges form and break very rapidly, pulling the actin filament along, shortening the sarcomere and causing the muscle to contract.

When the muscle stops being stimulated, calcium ions leave their bindng sites and are actively transported back into the sarcoplasmic reticulum. This causes tropomyosin molecules to move back, blocking the actin-myosin binding sites again. The actin filaments slide back to their relaxed position, lenghtening the sarcomere.

1) Aerobic respiration:

• Most ATP is produced in oxidative phosphorylation in the mitochondria
• It requires oxygen so is good for long periods of low intensity exercise, e.g. a marathon

2) Anaerobic respiration:

• ATP is made rapidly by glycolysis
• The end product is pyruvate which is converted into lactate by lactate fermentation
• Lactate can quickly build up in muscles and cause muscle fatigue, but anaerobic respiration os good for short periods of high-intensity exercise, e.g. a 400m sprint

3) ATP-Phosphocreatine (PCr) System:

• ATP is made by phosphorylating ADP- adding a phosphate taken from PCr, producing creatine and ATP
• PCr is stored inside cells and the ATP-PCr system generates ATP very quickly
• PCr runs out after a few seconds so is used during short bursts of vigarous exercise, e.g. a tennis serve
• The system is anaerobic and doesn't form any lactate

Skeletal muscles are made up of two types of muscle fibres:

1) Slow twitch:

• Contract slowly and can work for a long time without getting tired
• Good for endurance activities
• Energy is released slowly through aerobic respiration so they contain many mitochondria and blood vessles that supply the muscles with oxygen
• Red in colour as they contain lots of myoglobin (protein that stores oxygen)
• Muscles you use for posture, e.g. in the back, have many slow twitch fibres

2) Fast twitch:

• Contract very quickly and only work for a short period of time before getting tired
• Good for short bursts of speed and power
• Energy is released quickly through anaerobic respiration using glycogen so they contain few mitochondria or blood vessles
• Whiter in colour as they don't contain much myoglobin
• Muscles you use for fast movement, e.g. those in eyes and legs, have many fast twitch fibres