3 - Generation and propagation of action potential

Question 1

What are the 3 structural classes of neurons?

What are the differences between them?

Answer 1

1. Multipolar
   - many dendrites and one long axon
   - major neuron type in the CNS
2. Bipolar
   - One fused dendrite + one axon
   - rare
3. Unipolar
   - One process extends from the cell body forms the central and peripheral processes, which together forms the axon,
   - mainly in PNS, commonly in dorsal root ganglia of spinal cord

Question 2

List the processes of AP.

Answer 2

1. Resting membrane potential
2. Threshold stimulus
3. Voltage-gated Na+ channels are triggered to open, causing depolarization by Na+ influx. (+ve feedback)
4. Rapid Na+ depolarizes the membrane but not reaching the Na+ eqm potential (+60mV)
5. Inactivation of Na+ channels, K+ channels start to open

(Absolute refractory period)

6. Repolarization is caused by efflux of K+ ions (high permeability), Na+/K+ ATPase also have some contribution
   (-ve feedback)
7. Hyperpolarization caused by K+ continuing to leave the cell
8. Voltage-gated K+ channels close and K+ equilibrate through leak channels.
9. Return to RMP.

Question 3

Compare graded potential and action potential.

Answer 3

1. Shape of potential:
   Graded: Non-fixed shape; depends on the strength of stimuli;
   Action: Stereotyped size and shape > Fixed size of AP for a given cell type.
   (Size of AP is determined by the density of ions channel, concentration of
   ions…)
2. Summative?
   Graded: summative
   Action: non-summative due to absolute refractory period
3. Magnitude?
   Graded: various
   Action: All or none principle. Once above the potential is above threshold, the
   AP will be generated.
4. Intensity of stimuli is graded by?
   Graded: Amplitude
   Action: Frequency of AP
5. Decremental?
   Graded: Yes
   Action: No, due to self-regeneration process

Question 4

Absolute refractory period = No AP could be generated due to the inactivation of sodium channel;

Relative refractory period =?
Briefly explain.

Answer 4

AP could be generated but a much stronger stimulus is needed since:

1. less functional Na+ channels available
2. The K+ efflux makes the cell more -ve.

Question 5

What are the 4 implications of refractory periods?

Answer 5

1. AP are not summative
2. Limited frequency of AP
3. AP generated in refractory period do not have stereotyped size
4. Propagation of AP down the axon unidirectional

Question 6

List examples of voltage-gated Na+ channels blocker.

State their respective actions.

Answer 6

Tetrodotoxin, Saxitoxin – binds to extracellular site of sodium channel

Lidocaine – binding site inside the pore of sodium channel.
It produces nerve conduction block only after
the channels conduct a train of action potential (open state) allowing lidocaine to gain access to its interior binding site. (The more opening / activation of the channel, the more likely to be blocked).

Lidocaine blocked the Nociceptive fibre C that are small axon with few sodium channel present that are more susceptible to the blockage.

Question 7

How does hyperkalemia and hypercalcemia affect the excitability of the cell respectively?

Answer 7

Hyperkalemia: more K+ outside cell, increases RMP, increased excitability

Hypercalcemia:
more Ca binds to the -vd charge on cell membrane, increased shielding effect to cell membrane and decreased tendency for Na+ channels to open >
increased threshold of AP
no change in RMP

Question 8

Tetany (i.e. muscle cramp) occurs in subjects with _________ due to increased excitability of motor nerves
(and muscles).

Answer 8

Hypocalcemia

Question 9

With hypercalcemia, subjects will experience __________ due to decreased neuromuscular excitability

Answer 9

muscle weakness

Question 10

What is accommodation?

Answer 10

decline in excitability of a neuron with a slow gradual depolarization or prolonged depolarization
e.g. hyperkalemia

Question 11

Give the reasons why No action potential is generated above the “usual threshold potential”.

Answer 11

1. Inactivation of Na+ channels

2. Increase in K+ conductance as the K+ channels remains open.

Question 12

_____________ is used to treat ventricular fibrillation caused by hyperkalemia

Answer 12

Calcium intravenous infusion

Question 13

What is saltatory conduction?

Answer 13

AP jumping from node to node

[Node of Ranvier = no myelination, highest density of sodium channel and Na/K ATPase]

Question 14

In myelinated nerves, the axon is wrapped around by the myelin sheath – composed of layers of ________ of
the supporting cell, insulating the axon from the surrounding tissue fluid.

In non-myelinated nerves, the axons are separated by the _______ of the supporting cells but still in communication
with the extracellular fluid for ion exchanges.

Answer 14

cell membrane;

cytoplasm

Question 15

What are the supporting cells in nerves?

Answer 15

Oligodendrocytes (CNS) and Schwann cell(PNS)

Question 16

Conduction speed of AP in nerves are determined by?

Answer 16

1. Myelination of axons
2. Diameter of axons

(3. Na+ blockers
4. Ionic composition of intra- and extra-cellular fluids)

NOT determined by strength of stimulus

Question 17

What is the disease in which nerves are demyelinated, which may cause decreased conduction velocity, frequency-related block and total conduction block?

Answer 17

Multiple sclerosis (CNS);
Guillain–Barré syndrome

Question 18

What are the causes of demyelination?

Answer 18

1. Autoimmune destruction of myelin sheath

2. Mechanical crush

Question 19

Discuss advantages of myelination of nerve fibers and why there is a need of periodic breaks
in the myelin sheath with the nodes of Ranvier.

Answer 19

Advantages:
1. More cost-effective with a reasonable number of nodes of ranvier (if have more nodes of Ranvier, more pumps and channels are used, thus more energy consumption )

2. Faster propagation of nerve impulses compared with continuous conduction in unmyelinated nerves of the same diameter

Periodic breaks:
there is a limit on how far the Na+ influx form an action potential can move down the length of axon

Question 20

Is the RMP affected by demyelination?

Answer 20

NO!

depends on
availability of voltage-gated Na+ channels to be opened in the upstroke of AP (the increasing slope) > demyelination has no immediate effect on channel distribution or number

Question 21

Explain the changes in membrane potential, and in the frequency and amplitude of the action potential when external [K+] is raised. How would these changes affect the excitability of neurons?

Answer 21

• Higher frequency and lower amplitude
• When external [K+] increases, the membrane is depolarized, and thus more closer to the threshold (higher baseline)
• Takes shorter time to depolarize, therefore easier to generate an AP
• Depolarization inactivates some voltage-gated Na+ channels and possibly open some K+ channels

*** Cells might experience a period of increased excitability , followed by decreased excitability due to accommodation (decline in excitability due to prolonged depolarization)