AP

Question 1

Describe the order of events of the AP

Answer 1

Rising phase => overshoot => falling phase => undershoot/afterhyperpolarization

Question 2

What are the overshoot and undershoot?

Answer 2

Overshoot is the when the inside of the membrane is positively charged relative to the outside.Undershoot or afterhyperpolarization is when the membrane potential is more negative than the RMP.

Question 3

What causes APs?

Answer 3

APs are caused by depolarization of the membrane beyond threshold.

Question 4

What is the meaning of saying that APs are “all-or-none”?

Answer 4

Once generator potential depolarizes membrane beyond a critical value (threshold) an AP with fixed size, shape and duration is generated, independently of the intensity of the stimulus. If the generator potential doesn’t cross the threshold, no AP is generated.

Question 5

What happens when you increase the magnitude of the depolarizing current injected in a neuron?

Answer 5

The AP firing rate increases as the depolarizing current increases. AP frequency encodes stimuli intensity/magnitude.

Question 6

Why is there a limit for spiking frequency?

Answer 6

Because of the refractory period - the brief period following APs during which it is more difficult to excite a neuron

Question 7

What are the differences between the 2 types of refractory period?

Answer 7

The absolute refractory period lasts for 1ms during repolarization and immediately afterwards and the inactivation of Na+ channels makes it impossible to generate new APs (infinite threshold). The Na+ channels only activate again after closing which is more probable at negative Vm. The relative refractory period lasts for several ms where the threshold is higher than normal due to the the increase permeability of K+ channels which underlies the under shoot. New APs can be generated if the stimulus is strong enough.

Question 8

What is the K+ current assuming the K+ permeability is 0.5S and Vm=E(Na+)?

Answer 8

I=g(Vm-E(K+))= 0.5*(62-(-80))=71mA

Question 9

Which ion is responsible for a 10.5mA current when AP is at its peak and g(ion)=0.1S?

Answer 9

Cl- => E(Cl-)= -65mV

Question 10

How’s the driving force for Na+ at -80 mV? Vm-ENa

Answer 10

-80-62=-142mV

Question 11

What happens if Na+ channels open, i.e. the membrane permeability for Na + increases? How will I(Na+) be?

Answer 11

Na+ rapidly flows inwards, increasing the Vm (rising phase)

Question 12

Which voltage will Vm approach as long as gNa+»gK+?

Answer 12

The GHK equation will be dominated by Na+ contribution and hence Em will approach E(Na+) and thus Vm will tend to +62mV (E(Na+)) - overshoot

Question 13

How can we account for the falling phase of the AP in terms of changes in membrane permeability and g(ion)?

Answer 13

g(Na+)=0 due to Na+ channels inactivation (absolute refractory period), stopping the inwards flow of Na+, and g(K+) increases due to the opening of voltage-gated K+ channels (apart from the leak channels), hence K+ will dominate GHK equation and Em=E(K+), therefore K+ will flow outwards (repolarization) and Vm tends to -80mV (undershoot - afterhyperpolarization)

Question 14

What forms the selectivity filter of the Na+ channel?

Answer 14

The 4 pore loops between segments 5 and 6 of the 4 domains of the Na+ channel.

Question 15

Why is segment 4 of the Na+ channel domains special?

Answer 15

It´s the voltage sensor which gates the channel.

Question 16

True or false: when depolarizing current crosses AP threshold, Na+ channels open.

Answer 16

False (channels do NOT have thresholds, it just increases their open probability)

Question 17

How is the rising phase of APs explained by Na+ channel kinetics?

Answer 17

On depolarization, Na+ channels open with little delay (explains why AP is so quickly), stay open for a short period of time (1ms) (explains why AP is so brief) and then inactivate (explains falling phase and absolute refractory period).

Question 18

What is the molecular model for the inactivation of Na+ channels?

Answer 18

Hinge-and-lid model

Question 19

Which channels does TTX block?

Answer 19

Na+ channels

Question 20

How can we account for the falling phase of APs? What are the channels responsible?

Answer 20

The falling phase is explained by the inactivation of the Na+ channels and the delayed increase in K+ permeability that speeds repolarization. The delay in K+ channel opening after the AP gave them the name of delayed rectifier K+ channels.

Question 21

What is the threshold?

Answer 21

It’s the specific value of Vm at which the net ionic current (INa+IK+IK-leak) just changes from outward to inward, depositing positive charge on the inside of the membrane

Question 22

What us the importance of the membrane excitability?

Answer 22

Allows AP regeneration and thus propagation without attenuation

Question 23

Why do axons normally only propagate APs in one direction (from axon hillock to axon terminal)?

Answer 23

Because the membrane just behind it’s refractory, due to the inactivation of Na+ channels and
concomitant increase in g(K+) underlying the afterhyperpolarisation.

Question 24

What determines AP conduction velocity?

Answer 24

How far the depolarisation ahead of the AP spreads. The farther the current goes down the axon, the farther ahead of the AP the membrane will be depolarised and the faster the AP will propagate.

Question 25

What determines how far the local currents spread?

Answer 25

The path of least resistance determined by the diameter and membrane ionic permeability of the the axon. The larger the diameter and the lower the number of open channels, the father away the current can travel and the faster the conduction speed.

Question 26

If AP condition velocity increases with increasing axonal diameter why don´t we have giant axons?

Answer 26

Myelin sheath insulates the axonal membrane increasing the resistance (decreasing leakiness) and allowing local currents to travel farther away, thus increasing transmission speed.

Question 27

What is ‘saltatory conduction?

Answer 27

In myelinated axons APs skip from node to node. Voltage-gated Na+ channels are clustered at the nodes of Ranvier and only here, where axonal membrane is not insulated, are APs generated.

Question 28

Why does internodal distance increase with increase axon size?

Answer 28

Because the bigger diameter means that currents can travel farther away to the next node.

Question 29

What is the spike-initiation zone (SIZ) and where is it located?

Answer 29

The SIZ is the part of the neuron where Na+ channels are present at sufficient density to generate APs in response to membrane depolarisation. It is often located at the axon hillock and , for sensory neurons, in the sensory nerve endings.

Question 30

What is orthodromic conduction?

Answer 30

Conduction from SIZ to axon terminal. Antidromic conduction is the reverse.

Question 31

How is input information (magnitude and duration) encoded in APs? And how is it transmitted in the synapse (output)?

Answer 31

APs are all-or-none. Every AP has the same amplitude and duration. Hence, the information in the signal is represented only by the frequency and number of APs, which represent the amplitude and duration of the input, respectively.
The graded nature of input signal is translated into a frequency code of APs at the SIZ. The total number of APs in a given period of time determines exactly how much neurotransmitter will be released by the cell.