L3-4: Action Potential I-II

Question 1

Describe depolarization, overshoot, repolarization, undershoot and hyperpolarization

Answer 1

• Depolarization: driving membrane potential in a positive direction
• Overshoot: membrane potential becomes too positive
• Repolarization: driving membrane potential in a negative direction towards RMP
• Undershoot/aka hyperpolarization: driving membrane potential in a negative direction away from RMP

Question 2

Excitable tissue in the body

Answer 2

• Nerve and muscle – cells produce electrical signals (receptor potential, synaptic potential and action potential) when stimulated

Question 3

States and gates of voltage-gated sodium channel that plays a role in AP

Answer 3

• Three states: closed/resting – where activation gate closed and inactivation gate is open, open – where both gates open, inactivated – where inactivation gate closes
• Two gates: activation gate, inactivation gate

Question 4

States and gates of voltage-gated potassium channel that plays a role in AP

Answer 4

• Two states: closed/resting and open

- One gate

Question 5

Effect of tetrodotoxin

Answer 5

• Voltage-gated sodium channel blocker

Question 6

Phase of APs

Answer 6

1. ) Resting
2. ) Depolarization/Rising phase of AP
3. ) Repolarization/Falling phase of AP
4. ) Undershoot/hyperpolarization
5. ) Resting

Question 7

Describe phases of AP

Answer 7

1. ) Resting: see RMP – permeability K&raquo_space;> permeability Na
2. ) Depolarization: d/t opening of activation gate of Na, Na rushes in down its concentration gradient making membrane less negative. Probability of more Na channels opening during depolarization increases longer cell is in depolarization phase – permeability to sodium is increasing and exceeds than of potassium by top of overshoot
3. ) Repolarization: d/t closing of inactivation gate of Na, Na unable to come in now. K+ channels are opened after a brief delay of strong depolarization, so K+ rushes out of cell down it’s concentration gradient – permeability of sodium decreases and is exceeded by potassium by RMP
4. ) Hyperpolarization/undershoot: K remain open cell gets close to EsubK d/t these channels being slow to close and undershoot passed RMP occurs, they eventually close. During this time when membrane is repolarized back to RMP, the Na activation gate closes (now both gates closed) and the inactivation gate opens – channel is still closed though – this is resting state of the channel
5. ) Resting: see RMP. Na/K ATPase pumps helps drive cell back to RMP

Question 8

Effect of local anesthesia (benzocaine, lidocaine)

Answer 8

• diffuses through cell membrane and binds to sodium channel preventing it from opening and therefore preventing depolarization and APs

Question 9

What is AP threshold?

Answer 9

• Lowest voltage or minimum depolarization required to drive sodium channels into fast positive feedback loop. Once threshold is reached, AP generation is no longer dependent on stimulation – you get a full AP. All or nothing concept

Question 10

Effect of hypocalcemia on AP

Answer 10

• Hypocalcemia causes the threshold for AP to move closers to value of RMP and therefore it takes less or in some cases nothing for generation of AP

Question 11

Effect of hypercalcemia on AP

Answer 11

• Causes threshold for AP to move further away from RMP values and therefore it takes more depolarization to generate AP

Question 12

Clinical manifestations of hypocalcemia

Answer 12

• Neuropsych symptoms
• Neuromuscular irritability
• CV symptoms
• Autonomic symptoms
• CATS of hypocalcemia: convulsions, arrhythmias, tetany, spasms and stridor – laryngospasm, carpopedal spasms

Question 13

Clinical manifestations of hypercalcemia

Answer 13

• Symptoms include fatigue, lethargy, muscle weakness and diminished reflexes. Pt can show mental confusion and with very high levels, a coma.

Question 14

Mechanism underlying effect of calcium on AP threshold

Answer 14

• External calcium influences threshold by changing sodium channel function/open probability, it doesn’t affect RMP as no calcium channels open then

Question 15

How to test for hypocalcemia during physical exam?

Answer 15

1. ) Chvostek’s sign: tap on facial nerve and facial muscles on same side with contract. Not very sensitive (absent in 1/3rd cases) nor specific (10% of people with normocalcemia)
2. ) Trousseau’s sign: inflate BP cuff to greater than systolic over arm and look for spasm of muscles in hand and forearm, more sensitive and specific

Question 16

Effect of hypoparathyroidism on action potentials

Answer 16

• Reduction of serum calcium and hypocalcemia – leads to carpopedal spasms, laryngospasm, respiratory failure – CATS: convulsions, arrhythmias, stridor

Question 17

Effect of hyperparathyroidism on APs

Answer 17

• Leads to elevated serum calcium and hypercalcemia. Symptoms include fatigue, lethargy, muscle weakness and diminished reflexes. Pt can show mental confusion and with very high levels, a coma.

Question 18

Compare and contrast absolute and relative refractory periods, describe mechanisms underlying these periods

Answer 18

1. ) Absolute: period of time where a new AP cannot be elicited. Mechanism: d/t Na channel inactivation. Stimulus cannot open a sufficient number of Na channels to cause a second spike because too many are in inactivated state
2. ) Relative: period of time after absolute refractory period during which stronger than normal stimulus is need to elicit a new AP. Mechanism: d/t delayed K channel opening and closing. There is maintained permeability to K d/t slow closing of these channels and so K ions departing the cell oppose the depolarizing effect, therefore it has to overcome this.

Question 19

Relationship between axon diameter, myelination and speed of AP

Answer 19

• Increase in axon diabeter, increase AP velocity

- Myelin=insulation, increased AP velocity

Question 20

Describe the difference between myelinated and unmyelinated nerves in terms of:

a. ) Where are the VG Na channels?
b. ) Which conducts more rapidly and why?
c. ) Which conducts more efficiently?

Answer 20

• a.) Only exist at Nodes of Ranvier in very high density
• b.) Conduction is fast since no wasting time generating APs in membrane covered by myelin, capacitance of myelinated nerve is lower than unmyelinated
• c.) Efficient since less membranes APs and less Na flows into cells so less work for Na/K pump

Question 21

Describe saltatory conduction

Answer 21

• Refers to APs only generated at nodes of Ranvier, which are only areas on axon where VG Na channels exist. AP generated at one node causes current flow between active node and next node. Once next node reaches threshold new AP is generated. AP appears to jump from node to node.

Question 22

Which cell types are responsible for myelination in the PNS and CNS?

Answer 22

• In PNS: Schwann cells

- In CNS: oligodendrocyte

Question 23

What part of the NS is affected by Guillain-Barre syndrome? Multiple sclerosis? Describe each

Answer 23

1. ) Guillain-Barre: Abs mistakenly attack PNS resulting in PNS demyelination. Leads to muscle weakness and paralysis. Over time, good recovery results d/t PNS remyelination. Cause is unknown, but often preceded by an infectious illness such as stomach flu or respiratory infection
2. ) Multiple sclerosis: Disease of CNS resulting in demyelination of CNS axons, also loss of support cells oligodendrocytes. Believed to be autoimmune in etiology.