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Flashcards in SESSION 5 Deck (46):

The action potential is often described as all- or- nothing.
What does this mean?

Action potential is dependent on whether the threshold is reached
If the threshold is reached then he potential will definitely fire
If the threshold is not reached then the potential will not be fired

All- or- nothing- no transmission or transmission of the same amplitude
Amplitude never changes but increasing the frequency can effect the type of threshold reached


Which ion channels are involved in generating an action potential?

Voltage gated sodium and potassium channels


Briefly describe the molecular nature of the sodium and potassium channels

Voltage gated 6 transmembrane domains
Number 4 is positively charges
Change in membrane potential and depolarisation
due to charge repulsion there is a conformational change which allows the pore to open and allow sodium in and potassium out


Define activation in terms of voltage- activated ion channel

Activated means the opening and closing of the channel ion as a result of the electrical membrane potential


Define inactivation in terms of a voltage- activated ion channel

Inactivation means ion impermeable
The inactivation can be thought of as a plug
Closure of the inactivation gate causes sodium flow through the channel to stop, causing membrane potential to rise
It will reactivate when hyperpolarisation occurs


Describe how ions move as a consequence of channel opening during action potential

Membrane depolarised:
- Sodium ion channels open
- Sodium influx

Repolarisation of action potential is a two stage process:
Stage 1:
- Sodium ion channels inactivate
- Sodium influx stops

Stage 2:
- Potassium ion channels open
- Potassium efflux

Hyperpolarisation- due to delayed closing of the potassium ion channels


If the Na+/ K+ pump were to be blocked, what would be the consequence for nerve conduction of a single action potential in a nerve fibre?

No consequence- ion concentration is such a minor change


If the Na+/ K+ pump were to be blocked, what would be the consequence for nerve conduction of a train of 1000 action potentials?

There will be nothing to return it to normal, very high intracellular ion
e.g. No sodium gradient thus an action potential cannot be generated

Na+K+ATPase is not required for action potential re- setting mechanism
However the pump is required to re- set the membrane potential when lots have been fired


Define the term absolute refractory period

The time between initially opening and the initial closing of the Na+ channels

No matter how strong the stimulus nothing will initiate an action potential


Define the term relative refractory period

The time to recover back to the resting potential

Potential for action potential if strong stimulus applied


Explain how the properties of ion channels lead to the absolute and relative refractory periods

ARP- nearly all the sodium channels are in the inactive state

RRP- sodium channels are recovering from inactivation, the excitability returns toward normal as the number of channels in the inactive state decease


How might a drug act to block the production of action potentials?

Competitive block
Blocking of nicotinic receptors through competitive blocking


Indicate how local anaesthetics act to block action potentials of peripheral nerves

Procaine is an example of an anaesthetic

Two types of channel blockers:
Hydrophobic pathway- pass through the plasma membrane when pores are open and block entry of ions
Hydrophilic pathway- can't pass through the plasma membrane so act as competitive blockers

The more channels that open, the more anaesthetic binds, remain bound during inactivation


Tetrodotoxin blocks voltage- gated Na+ channels
4- aminopyridine blocks voltage- gated K+ channels

What effect would you expect each to have on the action potential?

Sodium channel blocked
Sodium cannot enter the cell
Depolarisation will not occur
Therefore a threshold potential wont be reached
No action potential generated

4- aminopyridine
Blocks potassium channels
The membrane will repolarisation but take longer as the non- voltage gated dependent channels would open
ARP is increased therefore another action potential cannot be fired during this time


Explain how release of ACh from the motor nerve terminal causes an action potential in the skeletal muscle

When acetyl choline binds to the channel that will cause a non formational change in the nicotinic acetylcholine protein causing the pore to open
The pore is cation selective- allowing flow of both potassium and sodium at equal rebates
Normal membrane potential is close to potassium equilibrium potential- therefore the driving force for potassium ions to leave is less than it is for sodium to enter
Sodium influx therefore predominates- leading to depolarisation
It will try to reach reversal potential for this channel which is halfway between the Ek and Ena
Depolarisation past threshold will result in an action potential


What is the difference between the mechanisms of action of D-tubocurarine and succinylcholine at the neuromuscular junction?

DTC- a competitive blocker of nAChr
The blocker can be reversed by increasing the concentration of ACh
Since this is competitive inhibition the substance present at higher concentration is more likely to bind

SC is a depolarising blocker f nAChr
This activates the receptor
Thus keeps the membrane depolarised permanently


Explain equilibrium potentials for sodium, potassium, calcium and chloride

The conductance of the membrane to a particular ion is dependent on the number of channels for the ion that are open

If the conductance to any ion is increased the membrane potential will move closer to the equilibrium potential for that ion


How are membrane currents measured?

Voltage- clamp
The membrane potential is controlled and the currents flowing through the membrane is measured


Define refractory period

A period immediately following stimulation during which a nerve or muscle is unresponsive to further stimulation


Describe the basic structure of voltage- gated sodium and calcium channels

One alpha subunit to make a functional channel
Consisting of 4 homologous repeats
Each repeat consists of 6 transmembrane spanning domains

4th sub particle is positive- sensing the voltage field across the membrane
Changing a membrane potential changes the membrane field
Resulting in a conformational change within the channel
As a result the pore opens

When the pore is open it is susceptible to inactivation
An inactivation particle enters the pore
This inactivation particle acts like a plug, stopping the flow of sodium ions through the pore in the membrane
The plug can be removed from the membrane once it has hyperpolarised


Describe the basic structure of voltage gated potassium channels

Potassium ion channels have a similar verbal structure to that of sodium and calcium
Except that each 'repeat' of a K+ channel us up fact a separate subunit

Thus it is made of Four alpha subunits rather than one


List the order local anaesthetic block in

1) small unmyelinated axons
2) un- myelinated axons
3) large unmyelinated axons


What properties of the axon lead to a high conduction velocity?

1) axons diameter- wider diameter axons will conduct faster
2) the degree to which the axon is myelinated
3) high membrane resistance
4) low membrane capacitance


Explain how the action potential is conducted along an axon, with reference to the local current theory

A change in membrane potential in one part can spread to adjacent areas of the axon by local current spread

Conduction velocity is determined by how far along the axon these local currents can spread
When local current spread causes depolarisation of part of the axon to threshold than an action potential is initiated

The further the local current spreads down the axon the faster the conduction velocity


Define capacitance

Capacitance is the ability to store charge
This is a property of the lipid bilayer

A high capacitance takes more current to charge and can cause a decrease in spread of the local current


Define the membrane resistance

The membrane resistance depends on the number of ion channels open
The lower the resistance, the more ion channels are open, and the more loss of the local current occurs across the membrane - limiting the spread of the local current effect


What does the spread of local current depend on?

1) membrane resistance
2) capacitance

Increase resistance, increases the local spread, and the potential being carried further


What is the function of the myelin sheath?

Good insulator- causing the local circuit currents to depolarise the next node above threshold and initiate an action potential

Reduce capacitance
Increase resistance of the atonal membrane


Explain the structure of the myelin sheath

Have a structure of alternating protein and lipid bilayers
In peripheral nervous system, myelin sheaths may form up to 100 layers


Describe the formation of the myelin sheath

Greatly extended and modifies plasma membrane wrapped around the nerve axon in a spiral fashion

Formed of special cells:
- the Schwann cells - myelinated peripheral axons
- oligodendroglial cells - myelinated axons in the central nervous system

Nodes of ranvier- periodic interruptions where short portions of the axon are left uncovered by myelin


Explain how myelination increases conduction velocity

Increase in membrane resistance
Decrease in membrane capacitance
Increase length constant
Decrease in time constant


State diseases affecting conduction of the action potential

Central nervous system:
- multiple sclerosis- all CNS nerves
- Devic's disease- optic and spinal cord nerves only

Peripheral nervous system
- Landry- Guillian- Barre syndrome
- Charcot- Marie- tooth disease

These disease result from the breakdown/ damage of myelin sheath
Multiple sclerosis is the most common


Explain how an action potential is generated

Depolarisation to threshold triggers the opening of many voltage- gated sodium channels
Influx of sodium ions produces the rapid upstroke of the action potential
This depolarisation causes inactivation of sodium channels and opening of voltage- gated potassium channels
Sodium influx stops and the increased potassium efflux leads to repolarisation


Explain how action potentials open calcium channels

Nerve terminal has a high density of voltage gated calcium channels
Depolarisation opens these voltage gated calcium channels
Calcium ion influx
Internal concentration of calcium increases
Causing a neurotransmitter to be released
--> (calcium ion channels are located close to vehicle release sites)

Because the concentration of calcium inside is so low, the calcium influx through calcium channels can raise the internal concentration of calcium significantly


Describe the basic structure of voltage gated calcium channels

Only one peptide is required to make a function channel (similar to the structure of sodium)

Other associated subunits enables correct regulation of channel activity
These associated subunits bind to the pore forming subunit, using through phosphorylation


Define neuromuscular junction

The synapse between a nerve and a skeletal muscle fibre


Describe events underlying fast synaptic transmission

- Calcium ions enter through calcium channels
- Calcium ions bind to synaptotagmin
- Vesicles brought close to membrane
- Snare complex make a fusion pore
- Transmitter released through this pore


Describe some properties of ligand gated ion channels

Nicotinic ACh receptor channels are ligand gated ion channels --> acetyl being the ligand

- acetylcholine binding to the receptor causes a conformational change
- as a result the channel opens
- the pore is cation selective- allowing sodium and potassium through at equal rates
- normal membrane potential is close to potassium equilibrium potential
- therefore the driving force doe potassium ions to leave is less that it is for sodium to enter
- sodium influx therefore predominates- leading to depolarisation
- it will try to reach reversal potential for this channel which is halfway between Ek and Ena
- depolarisation past threshold will result in an action potential


Describe how end plate potential initiates a muscle action potential

ACh binds to nicotinic ACh receptor on the post- junctional membrane to produce an end- plate potential

depolarisation will activate adjacent Na+ channels due to local spread of charge causing a muscle action potential

The action potential initiates contraction of the skeletal muscle fibre

Increased action potential increases ACh release- increasing contraction


Explain how neuromuscular blockers work

Competitive blocker- a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor
E.g. Tubocacarine
D- TC attaches to the receptor instead of ACh
The effects however can be undone by increasing ACh conc

Depolarising blocker- a form of neuromuscular blocker that depolarises the motor end plate (feeling paralysed)
E.g. Succinylcholine
Binds to nicotinic receptors activating them
But not broken down by esterase
Resulting in a single prolonged contraction
Depolarisation is required for another action potential to occur


Explain why myasthenia graves causes weakness

Myasthenia graves- autoimmune disease targeting nACh receptors

- patients suffer profound weakness- increases with exercise
- produce antibodies that block/ damage muscle receptor cells of nACh
- antibodies lead to loss of functional nAChR by compliment mediated lysis and receptor degradation
- prevents message being passed from the nerve ending to the muscles- muscles don't contract and become weak
- end plate potentials are reduced in amplitude leading to virtually no action potential


Describe some aspects of calcium channel diversity and function

-Type L situated in muscle, neurones and lungs
- target of many drugs
- blockers include DHP, e.g. Nifedipine

- voltage gated calcium ion channels activate more slowly than voltage gated sodium ion channels
- calcium ion channels activate and inactive- but slower than sodium
- calcium ion channel inactivation is calcium ion dependent


What is the difference between nicotinic and muscarinic ACh receptors

NAChR produces a fast depolarisation because it is a ligand gated ion channel

MAChR produce a slower response because they are coupled to G-proteins which trigger a cascade of events in the cell


Define conduction velocity

Conduction velocity is calculated by measuring the distance between he stimulating electrode

Conduction velocity= distance/ time


Explain the advantage of saltatory conduction in myelinated nerve fibres

Local current spread is faster than action potential spread over the axonal membrane surface


Explain the difference between myelinated and unmyelinated conduction velocity

Velocity proportional to diameter

Velocity proportional to the square root of the diameter