Action potentials and synaptic transmission

Question 1

What constitutes a cell’s membrane and what is it’s purpose?

Answer 1

Phospholipid bilayer:

- allows separation of aqueous ions between extracellular and intracellular space

Question 2

What are the forms of proteins that play a role in the exchange of ions between the extracellular and intracellular spaces?

Answer 2

> Leak and Gated channels: respond to external stimuli or NTs
Pumps

Question 3

What are the 3 intracellular-extracellular pathways in an axon?

Answer 3

> Na+ (sodium) channels: leak and gated
K+ (potassium) channels: leak and gated
Na+/K+ - ATPase pump

Question 4

What are anions and cations?

Answer 4

> Anions: negatively charged ions

> Cations: positively charged ions

Question 5

What is the role of leak channels in the resting membrane potential?

Answer 5

> Higher concentration of K+ leak channels in most membranes and neurons

> Organic anions locked within the cell

• > negative charge in intracellular space
• attracts cations like Na+ and K+
• rejects anions like Cl-

=> Positive charge along extracellular space

=> Intracellularly: higher concentration of K+ ; fewer Na+ ; low concentration of Cl-
=> Extracellularly: higher concentration of Na+ and Cl-

Question 6

How do Na+/K+-ATPase pumps function and what is their role in the resting membrane potential?

Answer 6

Energy dependent mechanism -> uses ATP transformed into adenosine diphosphate and phosphate molecules

> Helps maintain concentration gradient

• K+ > Na+ intracellularly
• Na+ and Cl- > K+ extracellularly

> Increases the concentration of Na+ in the extracellular space
Increases concentration of K+ in the intracellular space

=> Exchange of cations (3 Na+ pumped out and 2 K+ pumped in) helps to maintain the net negativity of the intracellular space compared to extracellular space

Question 7

What are the ionic forces that play a role in the resting membrane potential?

Answer 7

> Electrostatic force: cations go towards anions through leak channels
Force of diffusion: ions want to move along their concentration gradients from an area of high concentration to an area of low concentration
- e.g. K+ is attracted to the extracellular space
- e.g. Na+ is attracted to the intracellular space

Question 8

How do the ionic forces influence Na+?

Answer 8

Both electrostatic force AND force of diffusion push Na+ into the cell
-> Na+ is very potentiated and ready to enter the cell when voltage-gated Na+ channels open

Question 9

How do the ionic forces influence K+?

Answer 9

Divergent forces:

• electrostatic force takes K+ inside the cell
• force of diffusion brings K+ outside the cell

Question 10

How do the ionic forces influence Cl-?

Answer 10

Divergent forces:

• electrostatic force pushes Cl- outside the cell
• force of diffusion attracts Cl- inside the cell

Question 11

What is the equilibrium potential?

Answer 11

The point for any ion where the net flux across the membrane is zero, due to the force of the electrostatically charged component and the force of the diffusion being equal to each other.

Question 12

What is the consequence of the ionic gradients on the electrostatic charge of the intracellular and extracellular spaces?

Answer 12

The intracellular space is relatively more negative then the extracellular space.

Question 13

What is the direction of travel from neuron to neuron?

Answer 13

Dendrites (presynaptic neuron) -> Cell body -> Axon initial segement (AIS) -> Axon -> Axonic terminals -> Synapse -> Dendrites (postsynaptic neuron)

Question 14

What are graded potentials?

Answer 14

Changes in potential of the membrane around the ion channels which can be positive or negative

> They diffuse in all directions (like drop of water)

• > rapid decay of the potential
• > 1 or 2 inputs won’t affect the cell itself -> we need a summation of different effects to get over this diminishing response in graded potentials

Question 15

What is the impact of K+, Na+ and Cl- on graded potentials?

Answer 15

> K+ and Na+ ions are positively charged -> cause a depolarisation of the postsynaptic cell
Cl- ions are negatively charged -> inhibit the likelihood of depolarisation

Question 16

How is an action potential triggered?

Answer 16

1. Presynaptic neuron releases NTs, which activates a graded potential
2. As it moves through the cell body, it diminishes rapidly
3. Arriving at the axon initial segment (AIS), if graded potential reaches the threshold value (-55mV), it will trigger the all or nothing event of action potential

Question 17

What happens when the presynaptic signal(s) triggers an action potential?

Answer 17

Rapid flux of ions.

Question 18

What happens when the presynaptic signal(s) doesn’t trigger an action potential?

Answer 18

> Decay of graded potential

> Cell returns to its resting membrane state

Question 19

What are the 2 ways by which a postsynaptic neuron can integrate signals from multiple inputs (up to 400)?

Answer 19

1. Spatial summation
   - based on the location of inputs around the dendrites and the cell body
   - > larger graded potential travels to the AIS and generates an action potential
2. Temporal summation
   - based on the timing of triggering either by a single presynaptic input or multiple ones
   - if the first and second graded AP were to fire quickly, they would be summed on top of each other and potentially allow the triggering of an AP

=> Spatial location and speed of inputs firing can significantly affect the AP propagation

Question 20

What are excitatory postsynaptic potentials (EPSPs)?

Answer 20

Changes that happen in response to cations (e.g. K+ ; Na+ ions), which move the membrane potential towards the triggering threshold for an action potential.

Question 21

What are inhibitory postsynaptic potentials (IPSPs)?

Answer 21

Changes that happen in response to anions (e.g. Cl- ions), which move the resting membrane potential towards a hyperpolarized state and further away from the triggering threshold.

Question 22

Why is there a rapid influx of Na+ into the cell when voltage-gated Na+ channels open?
What is the consequence on the intracellular space?

Answer 22

> Na+ is drawn to the negative charge of the intracellular space by both the electrostatic force and force of diffusion -> very potentiated
In response to electrical stimuli, voltage-gated Na+ channels open -> rapid influx of Na+ into the cell
-> making the intracellular space more positively charged

Question 23

What happens when voltage-gated K+ channels open?

Answer 23

The force of diffusion pushes K+ out of the cell, rendering intracellular space more negative
= hyperpolarizing response

Question 24

What is cell hyperpolarisation?

Answer 24

The inside of the cell becomes more negative.

Question 25

What is cell depolarisation?

Answer 25

The inside of the cell becomes more positive.

Question 26

What is the role of the axon initial segment (AIS)?

Answer 26

> Designed to trigger action potentials (with threshold value)
It has high concentrations of various types of channels
-> uniquely responsive to change and uniquely excitable

Question 27

What are the phases of the action potential?

Answer 27

1. Resting membrane potential
2. Depolarising stimuli (e.g. Na+)
3. Depolarisation reaches threshold
   - > Na channels open and Na+ enters neuron
4. Rapid Na+ entry depolarises neuron further
5. Na channels inactivate (0.5 ms after)
   - ‘inactivation phase’
   - > Na channels can’t flux Na+ anymore
6. Slower responding K+ channels open and K+ moves out of neuron (more slowly than Na+)
7. K channels remain open (close more slowly than Na channels) -> more K+ leaves the neuron -> hyperpolarizing it
8. Voltage-gated K channels close, some K+ enters cell through leak channels
9. Normal/resting membrane potential

Question 28

What are the 2 important periods in response to ionic changes?

Answer 28

Refractory periods: points at which the axon either can’t fire OR will find it more difficult to fire subsequent APs

1. Absolute refractory period: cannot trigger AP
   - results from inactivation of Na+ channels
   - lasts until the resting membrane potential is restored
   - > allows neuron to control its excitability
   - > prevents back propagation
2. Relative refractory period: can trigger AP but a greater stimulus is needed to reach threshold
   - results from the hyperpolarization phase
   - K+ channels, slow to close, allow more K+ to get out of the cell -> lower the membrane potential
   = more negative than the resting membrane potential

Question 29

What are the 3 functional states of ion channels?

Answer 29

> Closed (resting) state
Open (active) state
Inactive (refractory) state
- charge dependent mechanism blocks the pore

Question 30

Do all ion channels have all 3 functional states?

Answer 30

No

• voltage-gated Na channels have all 3
• voltage gated K channels have no inactivation (refractory) state

Question 31

How do Na channels change during an action potential?

Answer 31

1. Resting condition
2. Voltage-dependent activation of the gate
3. Depolarisation phase
   - intracellular space has become positively charged with Na+ influx
4. Na channel is blocked, preventing further depolarisation (mV peak)
5. Hyperpolarization phase
   - normal membrane potential is restored
   - intracellular space is once again negative
   - Na+ channel is back to its resting condition, ready to fire the next AP

Question 32

How does the action potential conduction takes place across the axon?

Answer 32

1. Graded potential above threshold reaches the AIS
2. Voltage gated Na+ channels open and Na+ enters the neuron
   - AIS has high concentrations of voltage gated Na+ and K+ channels
   - > as Na+ and K+ channels trigger and open, they will further open more Na+ and K+ channels -> cause a rapid influx/depolarisation
3. Na+ depolarises membrane, further opening more Na+ channels
4. Depolarisation spreads along the axon
   - intracellular space becomes positive with rapid influx of Na+
5. K+ channels open, depolarising the membrane
   - K+ leaves cell -> intracellular space is more negative
6. Na+ channel inactivated (prevent back travel)

Question 33

How is the action potential conduction on non-myelinated axons?

Answer 33

Relatively slow process

• sequential voltage dependant channels have to respond along the entire length of the axon
• > each time the cycle has to refresh itself along the axon

Question 34

How is the action potential conduction on myelinated axons?

Answer 34

Incoming signal causes Na+ influx at the AIS
-> depolarisation -> positive charge spreads along axon to the next node of Ranvier where it can flux ions across membrane

> Saltatory conduction: no sequential activation of ion channels -> rapid increase of conduction velocity

Question 35

What happens to the action potential conduction in demyelinating disorders?

Answer 35

Demyelinating disorders (e.g. multiple sclerosis):

• breakdown of the insulating sheath
• > charge leaks out and AP dissipates across membrane because the membrane resistance is decreased
• > ongoing charge along axon is significantly reduced and if the potential is not strong enough to reach the adjacent node of Ranvier (next to AIS), AP will be lost

Question 36

What are the steps of synaptic transmission in chemical synapses?

Answer 36

1. Resting synapse
2. Action potential arrives, voltage-gated Ca2+ channels open
3. Ca2+ entry triggers exocytosis of synaptic vesicle content
4. NT diffuses across the synaptic cleft and activates ligand gated ion channels in the postsynaptic cell membrane

Question 37

What are the components present in chemical synapses?

Answer 37

> Voltage-gated Ca2+ channels
Mitochondria
Vesicles containing NTs
Ligand-gated ion channels

Question 38

What are the different mechanisms that deal with the removal of NTs from the synaptic cleft?

Answer 38

1. Reuptake of the NTs into the presynaptic cell
2. Reuptake of the NTs by the supporting glial cells (e.g. astrocytes)
3. Degrading of NTs on the postsynaptic membrane
4. Diffusion of NTs away form the synaptic cleft and taken up into the bloodstream

Question 39

How does a presynaptic action potential provoke an excitatory postsynaptic potential?

Answer 39

1. Incoming action potential
2. Action potential triggers a voltage change at the presynaptic terminal
3. Voltage-gated Ca2+ channels open and Ca2+ floods into the presynaptic terminal
   (high concentration of Ca2+ extracellularly)
4. This triggers vesicle exocytosis
5. Postsynaptic ion channels are activated and this allows Na+ to flux into the postsynaptic dendrite
6. Triggering of an EPSP (due to Na+ depolarising effect)

(triggering of IPSP if its Cl- channels)