Neuronal Excitability (Action Potentials)

Question 1

how does a nerve cell respond to a stimulus?

Answer 1

neurone is activated- its membrane potential will depolarise from RMP

Question 2

what is a graded depolarisation?

Answer 2

graded depolarisations of the membrane:
the level of depolarisation will be proportional to the strength of stimulation applied

Question 3

what happens if the membrane is continuously depolarised?

Answer 3

if the membrane is sufficiently depolarised to a certain critical level of membrane potential, it will suddenly generate an all-or-none event known as an ‘action potential’

Question 4

what factors determine the movement of ions during RMP, depolarisation and AP?

Answer 4

concentration differences of ions between intra-
& extra-cellular compartments of the cell are the
source of energy for movements of ion in nerves at
RMP

Question 5

define efflux and influx

Answer 5

the movement of ions in the cells is usually called flux:
influx: inward movement into the cells
efflux: the outward movement

Question 6

what factors effect the movement of ions (flux) across the membrane?

Answer 6

chemical gradient
electrical force

Question 7

how does chemical gradient effect movement of K+ and Na+ across the PM?

Answer 7

there is an unequal ion distribution so ions will flow down their concentration gradient
K+ concentration is higher inside driven to leave cell through ion channels (efflux)
Na+ concentration is higher outside- driven to enter cell through ion channels (influx)

Question 8

how does chemical gradient effect movement of K+ and Na+ across the PM?

Answer 8

ions are charged (Na+/K+) thus are attracted by voltage inside cell (Em)
At negative Em, drive for K+ and Na+ to move into the cell (influx)

Question 9

what does driving an ion across the membrane electrically require?

Answer 9

• the membrane possesses channels permeable to that ion to provide conductance
• there is an electrical potential difference across the membrane

Question 10

define equilibrium potential (Em)

Answer 10

The voltage of the membrane potential necessary to perfectly oppose the net movement of an ion down its concentration gradient - i.e. the Ion is in equilibrium (no net flux)

Question 11

how is an equilibrium potential achieved?

Answer 11

Different ions have different concentrations on either side of the membrane and the Chemical force will be different for each ion. Therefore, the membrane potential that must be achieved to equalise the two forces will be different. So, each ion has its own equilibrium potential.

Question 12

what happens to equilibrium potential if the membrane is permeable to only one ion?
where in the body does this happen?

Answer 12

the resting membrane potential will be equal to the equilibrium potential for that ion.
true for skeletal muscle cells and glial cells within the nervous system- their membranes are permeable to K+ only and so their membrane potential is equal to the equilibrium potential for K+

Question 13

what is the Nernst equation?

Answer 13

can be used to calculate the membrane potential at equilibrium for each of the ions in question

Question 14

why is the resting membrane potential closer to EK than ENa?

Answer 14

At rest the amount of Na+ entering is the same as K+
leaving, but because the permeability to K+ is much greater the resting membrane potential is much closer to EK (equilibrium potential of K+)

Question 15

define ionic driving force and when is it present?

Answer 15

the net force resulting from chemical (conc. gradient) and electrical influences (attract to opposite charge)
driving Force is present whenever Em is different from equilibrium potential for the ion (i.e. Em - Eion ≠. 0- this equation is how you calculate driving force for an ion)

Question 16

what happens to K+ and Na+ when Em is -65mV?

Answer 16

Em is approx. = -65mV
- If Em ≠ EK then the influences on K+ movement are unequal
- At -65 mV the chemical influence (efflux) is greater than the electrical influence (influx) so the ionic driving forces causes a net movement K+ out of the cell (efflux)
- Em ≠ ENa at -65 mV so both chemical and electrical influences result in an ionic driving forces which causes Na+ to move into the cell (influx)

Question 17

at -65mV, what is the permeability of the membrane to ions?

Answer 17

• there are more K+ leak ion channels than Na+ leak channels (as Em is -65 which is close to Ek rather than ENa)
• at rest the permeability of K+ is around 40 times that of the permeability of Na+ (PK = 40 x PNa)
• as there are more non-gated K+ channels, it has more influence in setting membrane potential: membrane potential (Em) controlled (mostly) by K+ movement).

Question 18

at -65mV, what is the driving force of the membrane to ions?

Answer 18

Na+ influx: due to both chemical gradient and electrical force
Na+: Large Driving force ( -65mv – 62mv = -127mv)
K+ efflux: Chemical gradient (causing efflux) is greater than electrical force (causing influx)
K+: Small Driving force (-65mv - -80mv = 15mv)

As the Em is at rest (voltage is constant) so Na+ influx must equal K+ efflux - achieved by: (look at table)

Question 19

what is the Em in neurones?

Answer 19

K+ efflux (trying to bring Em to -80 mV - EK)
Na+ influx (trying to bring Em to +62 mV - ENa)
So, Em must rest between EK and ENa

Question 20

what is the Goldman equation?

Answer 20

• equation is a modification of the Nernst Equation
• allows you to calculate Em whilst taking into account relative permeabilities of ions in question
• important modification because ion channels can modulate their permeabilities to ions

Question 21

briefly explain the process of how membrane potential changes throughout a neuronal excitation

Answer 21

1. A neurone (with a resting membrane potential: -65mV) is stimulated at one end causing its membrane potential to become less negative.
2. Membrane potential has to get to a voltage level less negative than the threshold value to generate an action potential.
3. Then there is a steep rise in membrane potential during depolarisation where the voltage increases up to +40mv.
4. The voltage then steeply goes down (repolarisation).
5. For a short time the membrane potential becomes more negative than resting potential (hyperpolarisation) before coming back to resting membrane potential.

Question 22

what is conductance (g) and what is it used for?

Answer 22

It is difficult to measure permeability so conductance is used as a measure instead. Conductance represents the activity of the ion channels.
Conductance (g) is directly proportional to how many channels are opening in the membrane (permeability does not have such a simple relationship)
Membrane acts as an electrical resistor (R)
Conductance, g = 1 / R (i.e. greater the resistance, the lower the conductance)
Each ion has its own conductance (gK; gNa)
Change in g for one ion results in a change in Em- this is due to changes in amounts of charge (ions) inside the cell

Question 23

how does voltage gated ion channel opening explain change in Em during an AP?

Answer 23

• at resting Em (-65 mV) Na+ influx = K+ efflux via leak channels
• voltage gated ion channels are closed at the resting membrane potential; Depolarisation = open; Repolarisation = close
• the more depolarisation the more ion VG ion channels open
  Initial Stimulus (depolarisation) causes the opening of voltage gated ion channels

Question 24

what happens during depolarisation of the membrane?

Answer 24

1. an initial stimulus opens the voltage-gated Na+ ion channels (i.e. increases (gNa)) which results in Na+ influx (in addition to that via ionic driving force) causing depolarisation.
2. if this becomes more positive than the threshold potential an action potential will be generated.
3. as you get further depolarisation you get the opening of more vg sodium ion channels so an even higher gNa.
4. Em rapidly approaches ENa - -doesn’t reach it due to leak k+ channels in membrane, it would only reach it if no other ion was influencing membrane potential.

Question 25

what happens during repolarisation of the membrane?

Answer 25

1. Na+ channels inactivate (don’t exactly close because stimulus to open them - still present) which turns off the channels and lowers sodium influx lower gNa and pNa
2. voltage gated K+ channels open (due to depolarisation) (higher gK and pK) a short while after Na+ ion channels
3. this results in K+ efflux (in addition to that via non-gated channels).
4. this leads to rapid repolarisation occurring and the Em becoming more negative.
5. for a short time the membrane potential becomes more negative than the resting potential (approaching Ek) -Hyperpolarisation.
6. the VG k+ ion channels then inactivate and Em returns to resting value due to leak ion channels (these are the only channels left controlling membrane potential as the other have been closed or inactivated) bring the Em back to -65mV)
7. NOT PUMPS, pumps would not detect an Action Potential as the no. of ions flowing during an AP is so small pumps would not detect a change in conc. inside the cells.

Question 26

when do leak channels control Em?

Answer 26

in the absence of the activity of gated ion channels, non-gated (leak) channels will control Em

Question 27

what causes initial depolarisation?

Answer 27

• synapses - they trigger depolarisation which open the channels
• generator potentials in sensory neurones - detect touch, pain etc. which will produce a change in membrane potential to open the channels.

Question 28

what channel opens first during depolarisation and why?

Answer 28

• Na+ channels open more quickly in response to depolarisation than K+ channels.
• If they both opened at the same time, there would be competition in producing a change in membrane potential. - Na+ channels open first to allow depolarisation, then K+ open to allow for repolarisation due to K+ ions leaving the cell. - Delayed moment so the channels opening/closing does not overlap (see graph)

Question 29

explain the graph

Answer 29

Orange line = is the action potential showing depolarisation, repolarisation and hyperpolarisation.
Solid Blue line = Change in conductance of the voltage-gated Na+ ion channels
Dashed green line = Change in conductance of the voltage-gated K+ ion channels
It is starting from 0 as leak channel activity is not shown (not actually 0) In terms of voltage gated activity g = 0 at resting membrane potential
Membrane potential never reaches either equilibrium potentials

Question 30

Why does Em approach ENa?

Answer 30

constant field equation = The Goldman current equation
- quantitative explanation of membrane potential approaching equilibrium potential for Na.
- using Goldman equation and factoring in that relative value, membrane potential = +40mV.
- qualitatively: A lot more Na+ channels than K+ channels, open at the peak of an action potential. This leads to Em of +40mV after depolarisation

Question 31

what is threshold?

Answer 31

the membrane potential where sodium influx is greater than potassium efflux, and therefore an action potential can be generated
- if the threshold value is reached an action potential will always be created and there will be a response to the initial stimulus.
- if the threshold is not reached, no action potential will be triggered and there will be no response.

Question 32

how does movement of ions allow for the threshold to be met?

Answer 32

• you may think all you need to open is one Na+ ion channel in order for Na+ influx to be greater than K+ efflux (and therefore the threshold value to be reached) as initially at Em they are the same
• however the depolarisation process reduces passive Na+ influx via leak ion channels (reduced driving force) and increases K+ driving force so you need to open many Na+ ion channels to have a greater Na+ influx than K+ efflux
• so the initial stimulus needs to be large enough to allow for enough Na+ voltage gated ion channels to open to ensure Na+ influx is greater than K+ efflux
• this allows for depolarisation and the threshold to be reached and thus resulting in a response

Question 33

what are the two types of refractory periods?

Answer 33

absolute
relative

Question 34

what is absolute refractory period?

Answer 34

not possible for another action potential to be generated by any size of stimulus (otherwise they happen too regularly and fast). this is because:
most VG Na+ channels inactivated – no further depolarisation
many VG K+ channels are open
not possible for Na+ influx to be greater that K+ efflux.

Question 35

what is relative refractory period?

Answer 35

can get another AP but you need a larger stimulus (greater threshold value)
Na+ channels are recovering from inactivation
some K+ channels still open – prevents depolarisation
here enough Na+ ion channels have recovered and enough K+ have closed for there to be the possibility of sodium influx to be greater than potassium efflux and so an another action potential to be generated.

Question 36

what condition does Na+ and K+ need to be in to generate AP?
what happens at the end of relative refractory period?

Answer 36

• to generate an AP we need to satisfy the condition -where Na influx is greater than K efflux -cannot satisfy this in absolute.
• once you get to the end of the relative refectory period all VG Na+ channels have recovered and VG K+ ion channels have closed so you are back to the resting state and the normal threshold value.
• so over this period of time the threshold value is decreasing.

Question 37

how is the strength of a response increased?

Answer 37

the strength of the response can be increased by increasing the firing frequency of action potentials
the magnitude of an AP cannot be increased

Question 38

where in the neurones is an AP generated?

Answer 38

when an action potential is generated in the neurone, it is only generated in part of the cell usually at the start of the axon it then propagates down the axon. This is slow

Question 39

explain the propagation of AP in an unmyelinated axon

Answer 39

Electrotonic spread - happens in unmyelinated axons
Region of the axon which has +ve charge = Action Potential
Where the AP has been or is going to go next is -ve as it is at the resting potential.
Once sodium ions are inside the axon, they are attracted by the negative charge and the concentration gradient ahead and behind so diffuse down along inside the axon.
Moving forward the Na+ ions begin to cause depolarisation triggering the opening of sodium voltage-gated channels a little further along the axon. This results in further influx of sodium ions from outside the membrane into this region causes depolarization and generate an action potential.
However the Na+ that diffuse backwards won’t cause another AP because this section is in its absolute refractory period and the Na+ channels are inactivated.

Question 40

what is the myelin sheath and what does it do?

Answer 40

Myelin sheath insulates sections of the axon
This increases speed of AP conduction
Insulation also means there is no leakage of charge which means action potentials can travel much further.

Question 41

explain the propagation of AP in an myelinated axon

Answer 41

In the CNS oligodendrocytes form myelin while the Schwann is used in the peripheral.
Myelinated axons transfer electrical impulses much faster than non-myelinated axons.
This is because only at the nodes of Ranvier do sodium ions enter the axon, causing depolarisation and generating the action potential.
The action potential ‘jumps’ from one node to another (by the flow of the ions) in a process known as saltatory conduction.
This is much faster than a wave of depolarisation along the whole length of the axon membrane as every time channels open and ions move it takes time, so reducing the number of places where this happens speeds up the action potential transmission.

Question 42

name a demyelinating disease

Answer 42

Multiple sclerosis

Question 43

what do conduction velocities depend on?

Answer 43

Myelination:
Unmyelination -0.1 meters/sec
Myelinated -100 metres./sec
Diameter:
The larger the diameter of the axon, the faster the conduction