Session 5 - Electrical excitability: Action potentials and the neuromuscular junction Flashcards
Outline 5 properties of an action potential
- change in voltage across membrane
- Depends on ionic gradients and relative permeability of the membrane
- Only occurs if a threshold level is reached
- All or nothing
- Propagated without loss of amplitude
Is the action potential in all excitable cells the same?
No, the action potential varies vastly from as axon to the Sino-atrial node. As a result of their ion different permeabilities
To produce an action potential how many ions need to move?
A relatively small amount relative to the charge
IE: in an axon of diameter 1 and 10 the [Na+]% change is 0.4% and 0.04% respectively
Describe the positive feedback loop when the membrane exceeds the threshold potential
- Depolarisation to threshold
- Voltage gated Na+ ions channels open
- Membrane is depolarised further stimulating more Na+ channels to open
This occurs until all the Na+ equilibrium is nearly reached and all the Na+ voltage gated channels are inactivated
Describe what happens during repolarisation of the action potential.
- Depolarisation
1) Opens voltage gated K+ channels and inactivated Na+ channel
2) This results in the efflux of K+ and the movement of Na+ is stopped
3) This repolarises the membrane
What role does the Na+/K+ ATPase pump have in an action potential?
The Na/K pump is NOT involved in the repolarisation it only restores the [K+] and [Na+] when hyperpolarisation occurs. It is crucial to realise that this deosn’t need to happen to allow for another AP only that it will occur over a relatively long time frame. (The concentration differences are so small as long as the membrane potential returns another AP can be formed)
Describe the Absolute and Relative refractory periods. Give relative times for these in a nerve.
ARP - During ARP no stimulus can initiate an action potential as all the Na+ voltage gated channels are inactivated. (1ms)
RRP - During the RRP a stronger than normal stimulus can initiate an action potential. This is because more Na+ channels are recovering from inactivation and K+ channels are closing (4ms)
What are the relative action potential durations and sizes in different tissues?
Axon: Duration = 0.5ms Size = -70mV to +30mV
Skeletal Muscle: Duration = 0.5ms Size = -90mV to +40mV
Sino-atrial Node: Duration = 100ms Size = -60mV to +30mV
Cardiac Ventricle: Duration = 100ms Size = -90mV to +30mV
Where on an axon are will an action potential be triggered if it exceeds the threshold and why?
Axon Hillock
This is where the sum of all the stimuli can be amounted (combination of small, large and inhibitory PSP)
What’s the difference between a Na+, Ca2+ and K+ voltage gated ion channel structure?
All have 4 homologous repeat units
Each repeat had 6 transmembrane domains 1 being voltage sensitive
Difference - Ca2+ and Na+ repeat units are bound together whereas K+ all 2 repeats are individual Alpha units
How do local anaesthetics work and give a named example?
Lidocaine - block Na+ channels to disrupt action potential propagation
1) transverses the membrane in it’s unprotonated form and either directly enters the channel or enters the cytoplasm
2) Becomes protonated and blocks the channel
In what order do local anaesthetics block axons?
1) Small myelinated axons
2) Unmyelinated axons
3) Large myelinated axons
?Why is it important Na+ channels are inactivated?
- To allow for the rapid switch off of the action potential
- Allows for inactivation of Na+ channels and as such a refractory period for propagation of an action potential
What is the consequence of the delayed closing of voltage gated K+ channels?
Ensures the hyperpolarisation of the cell to a larger degree which allows for faster reactivation of the Na+ channels
Why is Na/K pump NOT involved in producing the action potential?
Very little flow of ions. So there to maintain gradient.
What is the length constant with respect to an action potential?
the distance it takes for the potential to fall to 37% of it’s original value
What properties lead to a high conduction velocity?
1) A high membrane resistance
2) A low membrane resistance
3) A large axon diameter (low cytoplasmic resistance)
How does the myelin sheath act to increase the length constant?
The myelin sheath acts as a good insulator (by blocking the Na+ channels increasing the membrane resistance)
1) large increase in membrane resistance
2) large decrease in membrane capacitance
3) These increase length constant
4) slightly decrease in time constant
Why does multiple sclerosis effect people in many different ways?
The demyelination of the axons in the CNS can occur in any place there is no specific place as such it can effect people in many different way
What effect does demyelination have?
Demyelination decreases the length constant as resistance is decreased and capacitance is increased. This means that when the action potential reaches the next node it fails to reach the threshold and the AP is stopped.
Surmise action potential generation
1) Depolarisation to threshold triggers opening of many voltage gated Na+ channels
2) Na+ influx produces the upstroke of the action potential (membrane potential to ENa)
3) This depolarisation causes inactivation of Na+ channels and opening of K+ channels
4) Na+ influx stops and K+ efflux leads to repolarisation (potential to Ek)
5) relatively few ions move and Na/K pump NOT involved in repolarisation
Name some diseases that effect myelination and why the CNS and PNS are distinct diseases.
CNS - Multiple sclerosis (all CNS nerves)
- Devic’s disease - optic nerve and spinal cord
PNS - Laundy-Guilllian-Barre syndrome
- Charlotte-Marie-Tooth Disease
CNS and PNS are effected in distinct diseases as they are myelinated by different cells. CNS by oligodendrocytes and PNS by Schwann cells
What happens at the nerve terminal of a neuromuscular junction?
1- Action potential stimulates opening of Ca2+ voltage gated channels
2- Influx of Ca2+ ([Ca2+] increases)
3) stimulates the exocytosis (release) of neurotransmitter
What effect does the increased frequency of action potentials have on the nerve?
It increases Ca2+ influx and as such increased transmitter release (generating a greater stimulus)
What effect does the neurotransmitter have on the muscle end plate?
1) neurotransmitter (ACh) diffuses across cleft
2) ACh binds to nAChR which are lingand gated ion CATION channels
3) Depolarisation propagated along muscle as Na+ channels open
How does d-Tubocurarine work?
It blocks the nAChR by competitive inhibition. It can be overcome by increasing the concentration of ACh
How does succinylcholine work?
Succinylcholine inactivates Na+ channels resulting in the failure to propagate the depolarisation
Why is it so important to get general anaesthetics and neuromuscular blockers in the correct quantities for a surgery?
A person paralyzed with a neuromuscular blocker looks similar to a person under general anaesthetic - but though they will feel pain they are unable to speak or move.
What occurs in myasthenia gravis and how does the edrophonium test work?
This is an autoimmune disease which targets nAChR. As such end-plate potentials fail to reach threshold and trigger an AP.
Edrophonium chloride, a short acting anticholinesterase, allows ACh to act bind to greater proportion of receptors before being broken down and as such removes the symptoms
What is the effect of organophosphate poisoning?
They act as acetylcholinesterase inhibitors that form a stable and irreversible covalent bond to the enzyme.
As such this results in over stimulation of AChR.
Recovery takes weeks as new enzymes have to be produced to replace the effected ones
What is the difference between mAChR and nAChR and where are they found?
nAChR - fast depolarisation as it’s a ligand gated ion channel
mAChR - produced slower response as are linked to G proteins. They are found in the parasympathetic nervous target tissues
