1.6. The development of the action potential in excitable cells: similarities and differences between distinct cells. Conduction of the action potential. Flashcards

1
Q

I. Basics
1A. Definition of graded (electrotonic) potential?

A

A localized change in the membrane potential in response to a stimulus, which its size and duration proportional to the stimulus
- The distance over which the change in the potential decreases to a factor of 1/e of its maximal value is called the length or space constant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

I. Basics
1C. What are the definitions of depolarization, hyper polarization and repolarization?

A

1/ Depolarization -> bring the membrane potential closer to firing (more positive)
2/ Hyperpolarization -> brings the membrane potential less likely to depolarize (more negative)
3/ Repolarization -> restores the difference in charge between the inside and outside of the cell membrane following depolarization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

I. Basics
2A. What is the definition of AP?

A

a rapid, transient, self-propagating electrical excitation in the plasma membrane of an excitable cell (ex: nerve or muscle cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

I. Basics
2B. What are the characteristics of AP?

A

It is characterized by a rapid depolarization followed by repolarization to the resting membrane potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

I. Basics
3. What the 3 ways that AP differ from other responses?

A

1) AP has a much larger amplitude
2) AP is generally propagated down the entire length of the axon without decrement (dying out)
3) AP is an ‘’all-or-none’’ response (becomes either a full-sized AP or fails to become one)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

I. Basics
4. Make a comparison between AP and graded potential

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

I. Basics
5. What is the length/space constant?

A

Space or length constant is the distance over which the change in the potential decreases to a factor of 1/e of its maximal value

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

II. Development of action potential
1. What is the General mechanism of AP development?

A

Generally, action potentials develop as the result of a graded (electrotonic) potential which reaches the threshold voltage and stimulates a coordinated sequence of opening and closing of voltage-gated ion channels
=> resulting in depolarization and repolarization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

II. Development of action potential
2. What are the characteristics of voltage-dependent Na+ channel? (threshold voltage, activation and inactivation)

A

1/ Ethr = -50 mV
2/ Rapid activation
3/ Inactivation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

II. Development of action potential
3. What are the characteristics of voltage-dependent K+ channel? (threshold voltage, activation and inactivation)

A

Voltage-dependent K+-channel (delayed = low activation)
1/ Ethr = -50 mV
2/ Slow activation
3/ No inactivation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

II. Development of action potential
4A. How does AP develop in neurons? (7 steps)

A

1) At rest,K+- permeability is high and Na+-permeability is low, leading to a membrane potential of -70mV

2) Influx of positive charges causes a depolarization to reach the threshold potential of -50mV, and trigger an action potential

3) When the AP is generated, Na+-ions rush into the neuron as the voltage-gated Na+ channels open, while the voltage-gated K+ channels remain closed

During the depolarization phase, the neuron cannot transmit another impulse whatsoever = absolute refractory period (voltage-gated Na+ channels are inactivated)

4) When the Na+-ions almost stop rushing into the neuron, the voltage-gated Na+ channels become inactivated

5) At the top of the spike (+35mV to +40mV), repolarization occurs (restoring the negative charge inside the neuron) due to 2 mechanisms:
- Slow inactivation gates close on the same VG Na+-channels with a delay
- Opening of the VG K+-channels
6) The VG K+ channels remain opened
-> Causes excessive flow of K+-ions out of the neuron = causes only negative potential inside (hyperpolarization / afterhyperpolarization / undershoot) to -87mV
7) It can fire a 2nd action potential, but a stronger stimulus than normal is required = relative refractive period
- If there is no stimulus, the VG K+-channels close and membrane potential returns to resting value

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

II. Development of action potential
- AP development in neurons (7 steps)
4B. In step 5, At the top of the spike (+35mV to +40mV), repolarization occurs (restoring the negative charge inside the neuron) due to 2 mechanisms
=> What are these 2 mechanisms?

A

1/ Slow inactivation gates close on the same VG Na+-channels with a delay
2/ Opening of the VG K+-channels allow inward movement of K+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

II. Development of action potential
- AP development in neurons (7 steps)
4C. In step 6, The VG K+ channels remain opened
=> What are the consequences?

A

Causes excessive flow of K+-ions out of the neuron = causes only negative potential inside (hyperpolarization / afterhyperpolarization / undershoot) to -87mV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

II. Development of action potential
5. What is the definition of Absolute refractory period?

A

Due to closure of the inactivation gates of the voltage-gated Na+-channels, no new AP can form no matter how strong the stimulus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

II. Development of action potential
6. What is the definition of Relative refractory period?

A

Due to hyperpolarization via high K+-permeability through the slow K+-channels responsible for repolarization, any new AP formation would require a stronger than normal stimulus to reach the threshold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

III. Ionic basis of AP
1. What is the ion basis of AP?

A

I = current, g = conductance
Eion calculated by Nernst equation

I ion = g ion * (Em - Eion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

III. Ionic basis of AP
2A. This is the ion basis of AP
-> Interpret it.

A
  • The early phase of an AP is a result of a rapid increase in gNa, which causes the membrane potential to change toward the Eeq for Na+
  • Even though there is the rapid change in gNa, the gK/gNa ratio DOES NOT REACH 0
    -> Membrane potential is driven back toward Eeq for K+ and repolarizes towards its resting value
  • Afterhyperpolarization occurs, because gK remains high for a period of time after the AP
    -> As gK returns to its baseline level, the potential returns to its baseline level
18
Q

III. Ionic basis of AP
2B. the gK/gNa ratio DOES NOT REACH 0
=> Why?

A

1) Rise in gNa with depolarization is transient (short-term)
2) Depolarization leads to a rise in gK -> causes the ratio to stop falling and start increasing

=> Membrane potential is driven back toward Eeq for K+ and repolarizes towards its resting value

19
Q

III. Ionic basis of AP
3. What is the sequence of AP development based on ion basis?

A
20
Q

IV. Similarities and differences in AP between distinct cells - Cardiac APs
1A. What are the Characteristics of cardiac AP?

A
  • Longer duration: cardiac APs are longer than neuronal APs and range from 150ms in atria to 300ms in Purkinje cells
  • Plateau phase: cardiac APs display a depolarized ‘’plateau’’ phase due to slow Ca2+- channels
  • Longer refractory periods: due their longer duration (results from plateau phase)
21
Q

IV. Similarities and differences in AP between distinct cells - Cardiac APs
1B. What are the Phases of cardiac AP?

A
  • Phase 0 (upstroke)
  • Phase 1 (initial repolarization)
  • Phase 2 (plateau)
  • Phase 3 (repolarization)
  • Phase 4 (electrical diastole)
22
Q

IV. Similarities and differences in AP between distinct cells - Cardiac APs
1C. What happen in Phase 0 (upstroke) of cardiac myocytes APs?

A
  • Rapid depolarization due to increase in Na+-permeability.
  • Fast depolarization-induced activation gates on the Na+-channels open, followed by closure of slow depolarization-induced inactivation gates – resulting in a peak voltage of +20mV
23
Q

IV. Similarities and differences in AP between distinct cells - Cardiac APs
1D. What happen in Phase 1 (initial repolarization) of cardiac myocytes APs?

A
  • As Na+-channel inactivation gates close, slow depolarization-activated K+-channels open.
  • Both electrical + concentration gradients favor K+-efflux, and thus the membrane repolarizes slightly
24
Q

IV. Similarities and differences in AP between distinct cells - Cardiac APs
1E. What happen in Phase 2 (plateau) of cardiac myocytes APs?

A
  • During the upstroke phase, slow L-type VG Ca2+-channels (the dihydropyridine channel, or DHP channel) begin to activate. Ca2+ flows into the cell – counteracting the initial repolarization effect of K+-efflux leading to the voltage plateau.
  • Since the electrical + concentration gradients still strongly favor K+-efflux, K+-permeability cannot be too high or else the cell would repolarize without achieving a plateau.
  • Inward-rectifying channels decrease K+-permeability by closing at depolarized voltage, thus allowing this balance of flows
    => This Ca2+-influx also induces Ca2+-release from RyR channels on SR, to maintain excitation-contraction coupling, strengthening muscle contraction

**Note: The ryanodine receptors (RyRs) are a family of Ca2+ release channels found on intracellular Ca2+ storage/release organelles.

25
Q

IV. Similarities and differences in AP between distinct cells - Cardiac APs
1F. What happen in Phase 3 (repolarization) of cardiac myocytes APs?

A

As Ca2+-permeability decreases and K+-permeability increases, K+-efflux overcomes Ca2+-influx and the cell repolarizes

26
Q

IV. Similarities and differences in AP between distinct cells - Cardiac APs
1G. What happen in Phase 4 (electrical diastole) of cardiac myocytes APs?

A

membrane potential approaches K+-equilibrium potential, K+-efflux slows down and the cell comes to rest at its Em of -85mV

27
Q

IV. Similarities and differences in AP between distinct cells - SA node APs
2A. What are the Characteristics of SA node AP?

A
  • Upstroke + repolarization phases , but ionic mechanism differs
  • No stable membrane potential + no plateau
  • Has automaticity – which leads to the SA node’s spontaneous pacemaker activity
  • Less negative Em, partially because they do not have inwardly rectifying K+-channels
28
Q

IV. Similarities and differences in AP between distinct cells - SA node APs
2B. What are the Phases of SA node AP?

A
  • Phase 0 (upstroke)
  • Phase 3 (repolarization)
  • Phase 4 (pacemaker potential)
29
Q

IV. Similarities and differences in AP between distinct cells - SA node APs
2C. What happen in the Phase 0 (upstroke) of SA node AP?

A
  • Less rapid than in cardiac myocytes. Depolarization occurs slowly with Na+- influx via the ‘’funny channels’’ (If).
  • At the threshold voltage: T-type VDCCs and L-type VDCCs activate, and Ca2+-influx fully depolarizes the nodal cells
30
Q

IV. Similarities and differences in AP between distinct cells - SA node APs
2D. What happen in the Phase 3 (repolarization) of SA node AP?

A

As in cardiac myocytes, increased K+-permeability (due to mostly the delayed rectifier K+-current (IK)) repolarizes the cell to about -65mV

31
Q

IV. Similarities and differences in AP between distinct cells - SA node APs
2E. What happen in the Phase 4 (pacemaker potential) of SA node AP?

A
  • As repolarization continues, the cell potential reaches about -50mV, which triggers slow opening of inward Na+-channels – and the funny current begins to slowly depolarize the cell until the threshold potential for the upstroke is met again.
  • This is why SA node has automaticity and sets the HR.
  • If the rate of phase 4 increases, the SA node will fire more APs per unit time
32
Q

IV. Similarities and differences in AP between distinct cells - Skeletal muscle APs
3A. What are the characteristics of Skeletal muscle APs?

A

1/ Similar shape to neuronal APs, but slightly slower repolarization
2/ 5ms total duration

33
Q

IV. Similarities and differences in AP between distinct cells - Skeletal muscle APs
3B. What are the phases of Skeletal muscle APs? What happen in these phases?

A

1/ Depolarization: opening of VG Na+-channels
2/ Repolarization: closure of Na+-channels + opening of VG K+-channels
3/ Hyperpolarization: VG K+-channels

34
Q

IV. Similarities and differences in AP between distinct cells - Smooth muscle APs
4A. What are the characteristics of Smooth muscle APs?

A

1/ Compared to neuronal APs – smaller amplitude, longer duration and different ion currents (highly Ca2+-dependent!)
2/ Resting Em is not constant, but oscillates between -40 to -80mV, in so called slow waves, which are initiated by pacemaker interstitial cells of Cajal between the wall’s two muscular layers of f.ex. GI-tract
3/ Slow waves are conducted to the GI SM layers via gap junctions on processes of Cajal cells. Frequency from 3/min in stomach -> 12/min in duodenum
- Induce only weak contraction, but if voltage of the slow wave meets a threshold, APs may be triggered on top of the wave increasing the force of contraction.
- More AP peaks = stronger SM contractions

35
Q

IV. Similarities and differences in AP between distinct cells - Smooth muscle APs
4B. What are the ion mechanisms of Smooth muscle APs?

A

1/ Depolarization: L-type VDCCs
2/ Repolarization: late voltage-gated K+- channel
3/ Plateau phase: Ca2+-activated K+-channel

36
Q

V. Conduction of action potentials
1. What are the 3 steps of AP conduction?

A
  1. Initial segment is depolarized such that the cytosol Is positive; adjacent area remains at resting membrane potential
  2. Positive charges inside the initial segment flows down the axon to adjacent areas, and the positive charge outside flows oppositely
  3. Adjacent area depolarize to threshold, opening of ion channels and firing an AP. Initial segment repolarizes back to resting membrane potential
37
Q

V. Conduction of action potentials
2A. What are the 2 factors of AP conduction velocity?

A

1) Axon diameter
2) Myelination

38
Q

V. Conduction of action potentials
2B. How can axon diameter affect AP conduction velocity?

A

Larger axon diameter = higher conduction velocity because resistance is inversely proportional to cross-sectional area (R = V/CSA)

39
Q

V. Conduction of action potentials
2C1. What does myelin consist of?

A

Myelin consists of plasma membrane of certain cells that insulate the nerve fiber - Schwann cells (PNS ) and oligodendrocytes (CNS)

40
Q

V. Conduction of action potentials
2C2. How can myelination affect AP conduction velocity?

A

1/ Myelin increases the membrane resistance + decreases membrane capacitance
-> Less current is lost through the membrane per length of axon

2/ Unmyelinated nodes of Ranvier at 1-2mm intervals allow the necessary current to flow in/out for AP propagation
- the current ‘’jumps’’ at higher speeds between the nodes = saltatory conduction greatly increases the velocity
=> AP jumps from one node of Ranvier (unmyelinated part of axon) to the next

41
Q

V. Conduction of action potentials
3. What is the relationship between space constant and AP conduction velocity?

A
  • Space constant↑ = speed of propagation↑
  • RIC↓ = diameter of axon↑
  • Rmembrane ↑ - myelin
42
Q

VI. How is AP controlled?

A
  • Inhibitors of voltage-dependent Na+-channels (lidocaine)
  • [Ca2+]plasma ↑ = Ethr more positive
  • [Ca2+]plasma ↓ = Ethr more negative
  • [K+] – repolarization