Nervous System: Impulses and synapses

What is a resting potential?

When no impulse is present in the axon.

The inside is negative compared to the outside.

How is a potential difference created across the axon membrane?

By the distribution of charged ions

Give an example of something that facilitates membrane transport in the axon.

Sodium potassium pump

- 3Na+ in

- 2K+ out

These ions move in & out of the axon via active transport to maintain a resting potential

What happens in the sodium-potassium pump?

- The movement of sodium ions is against its concentration gradient, meaning there is more sodium ions extracellularly than intracellularly

- The movement of potassium ion intracellularly means there is more ions inside the axon.

- Due to 3 sodium ions moving out compared to 2 potassium ions in, the net movement makes the intracellular charge negative.

What happens to the sodium-potassium pump at resting potential?

- The sodium-potassium pumps are active, but sodium channels are closed to sodium cannot enter the cell

- Some of the potassium channels are open so potassium can naturally diffuse out of the axon.

- The means potassium ions can diffuse down its concentration gradient out of the cell via the potassium channels, transferring the positive charge extracellularly

- At rest, the neuronal membrane is 100x more permeable to potassium ions than sodium ions. Meaning there is a greater movement of K than Na at resting potential.

Besides from the sodium & potassium ion movement what other organic anions are there within the cell?

- glucose

- proteins

- amino acids

How does the presence of the organic anions cause a negative charge intracellularly and a positive charge extracellularly?

- The inside of the axon has an overall negative charge due to the presence of the anions which are unable to cross the plasma membrane

- Due to the negative state inside the axon there is an electrochemical gradient produced which causes potassium ions to be attracted to the inside of the axon.

- Because the force of the concentration gradient is stronger than the electrochemical gradient, there is an overall (net) movement of K+ out of the axon. Results in negatively charged intracellular space

- Resulting in a negative charge intracellularly and a positive charge extracellularly

What happens once the resting potential has been reached?

- No further movement of K+

- Potential difference across the axon is -70mV

- Axon is now polarised

- State is maintained until an impulse is present

What must happen to generate an action potential?

The stimulus must be a certain strength. It must be greater than the threshold value.

What is the all or nothing principle?

- If insufficient voltage-gated sodium channels open, the stimulus will be below the threshold. The axon will not depolarise.

- APs will be the same size regardless of strength of stimulus

- Speed of APs will also be the same regardless of stimulus

Weak stimulus

- sub threshold

- no action potential

Medium stimulus

- above threshold

- +35mV action potential

Strong stimulus

- above threshold

+35mV action potential

- frequency increased relative to medium stimulus

Action potential

- Can only be generated when a stimulus is greater than the threshold value

- Action potential is a temporary reversal of the potential difference in the axon

- This is achieved by voltage gated ion channels

What are the stages of an action potential?

1. Resting potential

2. Stimulus hits threshold

3. Depolarization

4. Repolarization

5. Refractory period

6. Return to resting state

Resting potential

- Neuron membrane is at rest

- Membrane is polarised

- Resting potential difference is at -70mV

- Voltage-gated Na+ channels closed

- Voltage-gated K+ channels closed

Stimulus

- Stimulus has reached threshold

- Membrane begins to depolarise

- Potential difference begins to increase (+ve)

- Voltage-gated Na+ channels open

- Voltage-gated K+ channels closed

- Inside of axon becomes more positive

Depolarisation

- Membrane is now depolarised

- Potential difference increased to +35mV

- The influx of Na+ causes more voltage-gated Na+ channels open

--> due to inside of cell being more positive

- Voltage-gated Na+ channels open

- Voltage-gated K+ channels closed

- Inside of axon is now more positive than extracellularly

- Action potential is propagated along the axon.

Repolarisation

- Membrane begins to repolarise

- Sodium channels close after ~0.5ms

- Voltage-gated Na+ channels closed

- Voltage-gated K+ channels open

- Potassium ions now diffuse out of axon lowering potential difference

- As more potassium ions move extracellularly, this causes more voltage-gated K+ channels to open

--> the flood of potassium outside of cell causes inside of cell to become more negative

Refractory period

- membrane is now hyper polarised

- potential difference reaches between -70mv to -75mV

- Voltage-gated Na+ channels closed

- Voltage-gated K+ channels open

- Voltage-gated K+ channels remain open causing too many K+ to leave the axon causing the inside os axon to become too negative (hyper polarised)

Return to resting state

- The neuronal membrane returns to rest

- The sodium-potassium pumps return the neuron to resting potential

- membrane becomes polarised

- Resting potential difference is at -70mV

- Voltage-gated Na+ channels closed

- Voltage-gated K+ channels closed

What does the refractory period do?

- Prevents an action potential being generated too quickly after initial stimulus

-> regulation of nerve impulses

- Nerve impulses move one-way only

- Limits number & frequency of nerve impulses

- At action potential, membrane is unexcitable for a short time

What are the three states in the refractor period?

- normal resting state

- absolute refractory period

- relative refractory period

What happens at the normal resting state?

- Axon is at normal resting excitability

- Action potential may be generated

What happens at the absolute refractory period?

- 1ms

- After an action potential generated

- No further impulse possible in region

- Stimulus strength irrelevant

What happens at the relative refractory period?

- 5ms

- Action potential may be generated

- Only if the stimulus exceeds higher than the normal threshold value

- If we have normal level of stimulus no AP generated

- If we have really strong level of stimulus an AP will be generated if it needs to

What are the factors that affect impulse speed?

- Axon diameter

- Surface area to volume ratio

- Temperature

- Rate of diffusion of ions across axon membrane

How does axon diameter affect impulse speed?

- Larger axons transmit faser impulses

How does surface area to volume ratio affect impulse speed?

- smaller axons have larger SA:Vol

- more ions leak out of axon

- harder to generate action potential

How does temperate affect impulse speed?

- higher temperature

- faster the speed of impulse

How does the rate of diffusion of ions across the axon membrane affect impulse speed?

- Species with more voltage gated channels --> higher rate

- Species with less voltage gated channels --> lower rate

What happens in an unmyelinated neuron?

A nervous impulse passes along the neuron as a wave of depolarisation.

What is the speed of the unmyelinated axon conduction velocity?

Can range between 0.5 to 10 m/s (dependent on neuron type)

What illness can be associated with unmyelinated neurons?

- Multiple sclerosis (MS) is associated with unmyelinated neurons of the CNS.

What is MS and how is it caused?

- A neurological disease that results in the deterioration of the myelin sheath on CNS neurons

- Where the myelin sheath has deteriorated it is replaced by hardened scars or plaques (scleroses). These can interfere with the transmission of nerve impulses, slowing them down & causing a gradual loss in motor activity.

What do myelinated neurons do?

- Impulses travel along the axon

- Function is insulation, protection and speeds up impulse.

- Action potential moves faster along myelinated neurons

What is the myelin sheath made up of in the PNS?

- Schwann cells

--> they wrap around the neuron

What is the myelin sheath made up of in the CNS?

- Oligodendrocytes

--> one oligodendrocyte can provide myelinth to multiple neurons.

What are nodes of ranvier?

- Regular intervals where the myelin sheath is interrupted

- The action potential moves from node to node in a process called saltatory conduction

What are synapses?

- Neurons don't touch eachother but a nervous impulse can transmit between neurons at junction called synapses

- The gap is bridged my chemical diffusion (of neurotransmitters)

Examples of neurotransmitters that diffuse across synapses

- Acetylcholine

- Noradrenaline

- Dopamine

- Serotonin

- Glutamine

What does the axon do?

Takes information away from the cell body

What does the presynaptic membrane do?

Contains neurotransmitters, mitochondria, organelles

What is the synaptic cleft?

The space between the pre/post synaptic membranes

What is the postsynaptic membrane?

Receptor sites for neurotransmitters

What does the dendrite do?

Receive information & deliver to cell body

What happens at a synapse?

1. Action potential travels along axon until it reached a pre-synaptic terminal

2. The depolarisation stimulates calcium channels to open

3. The influx of calcium ions cause vesicles full of neurotransmitters to migrate towards the pre-synaptic membrane

4. The vesicles then bind with the pre-synaptic membrane via exocytosis & releases the neurotransmitter into the synaptic cleft

5. The neurotransmitter then diffuses across the synaptic cleft to the post synaptic membrane

6. The neurotransmitter then binds to a lignand-gated sodium channel that is specific to that neurotransmitter

7. The ligand-gated sodium channel then opens allowing sodium to influx into the post synaptic neuron

8. The sufficient influx of sodium reaches the threshold value, an action potential is generated in the post synaptic neuron.

9 An enzyme in the synaptic cleft (specific to the neurotransmitter) then breaks down the neurotransmitter into its constituent components

10. The constituent components of the neurotransmitter is then reuptaken by the pre-synaptic membrane, either by passive diffusion of active transport via the process of endocytosis

11. Once inside the pre-synaptic terminal, the constituent components are then reformed into the respective neurotransmitter which requires ATP

What are voltage-gated ion channels?

- Ions that open and close depending on membrane potential

- Used in propagating an action potential

- They are selective so only open to one type of ion

What are ligand-gated ion channels?

- Respond to chemical signals rather than membrane potential

- Some activated by binding neurotransmitters

--> synaptic transmission

- Less selective so different ions can diffuse through them

Effects of neurotransmitters

- They may not always stimulate the post-synaptic neuron.

- But if they do the effect will be excitatory of inhibitory

What is the excitatory effect of neurotransmitters?

New action potential created in the post synaptic membrane

What is the inhibitory effect of neurotransmitters?

Less likely that a new action potential will be created in the postsynaptic neuron

What are the two types of drugs that bind with receptors on the post synaptic neuron?

Agonists and antagonists

What do agonists do?

- Bind to receptors & stimulate or enhance the neurotransmitters actions

> Are a similar shape to the neurotransmitter that is specific to the receptor

> So can bind to the receptor

What do antagonists do?

Block and inactivate receptors

What are SSRIs and what do they do?

- Selective serotonin reuptake inhibitors

- Common antidepressant drug

- Block reuptake of serotonin for half life of drug (2 weeks)

- Does this by blocking receptor so serotonin can't be reuptaken into presynaptic terminal

- So serotonin remains in cleft further triggering the next neuron

- Cell can detect serotonin in the cleft so it stops producing its own

- After patients stops taking SSRIs it can take the body a while to start producing its own serotonin again

Action of nicotine

Acetylcholine receptor agonist

Behaviour of nicotine

- Smokers: relaxation, alterness, decreased appetite

- Non-smokers: nausea, vomiting, diarrhoea

Action of alcohol

-reduced flow of Ca+ into cell

- GABA agonist

- Increased number of glutamate binding sites

- Interferes with secondary messenger sites

Behaviour of alcohol

- Low does is excitatory

- Moderate-high dose is inhibitory

Action of caffeine

- Modulated synaptic function by blocking adenosine receptors, inhibiting phosphodiesterase and mobilising intracellular calcium, ultimately influencing neurotransmitter release & synaptic plasticity

- reduces down regulation (reabsorption) of dopamine & glutamate

Behaviour of caffeine

- Increase DA leads to increased alertness & feeling good

What are the primary mechanisms of action?

- Acts as an adenosine antagonist

- Increased neurotransmitter release

How does caffeine act as an adenosine antagonist?

- Blocks adenosine receptors in the post-synaptic membrane, preventing adenosine from binding & exertion its inhibitory effects.

- By blocking adenosine, caffeine essentially reduces feelings of tiredness & promotes alertness.

- Because it hinders the reuptake of neurotransmitters

--> Adenosine normally promotes tiredness & regulates circadian rhythm

How does caffeine increase neurotransmitter release?

Caffeine can also hinder the reuptake of other neurotransmitters into the pre-synaptic membrane, such as dopamine, noradrenaline & glutamate.

Action of cocaine and crack cocaine

Blocks reuptake of dopamine & noradrenaline

Behaviour of cocaine and crack cocaine

- Feelings of well-being & confidence

- Reduced desire for sleep & food

--> because dopamine & noradrenaline stop you feeling sleepy

Action of opiates (heroin, morphine, codeine)

- Endorphin agonist

- Doesn't matter what opiates you take you body processes them all as morphine

Behaviour of opiates

- Pain suppression & euphoria

- Suppresses cough & diarrhoea

Action of LSD

serotonin receptor agonist

Behaviour of LSD

Visual hallucinations