Lecture 19: Ion Channels & Action Potentials Flashcards
(85 cards)
1
Q
Are there more leakage or voltage-gated Na+ channels?
A
Voltage-gated
2
Q
Are there more leakage K+ channels or Na+ channels?
A
K+
3
Q
What is necessary for a cell to depolarize?
A
Incoming Na+ ions must exceed leaving K+ ions
4
Q
What does the threshold voltage correspond to?
A
Voltage at which a cell will fire an action potential = voltage-gated Na+ channels are at equil with leakage K+ channels = critical number of voltage-gated Na+ channels opening to OVERCOME the K+ leakage channels
5
Q
What is important to note about action potentials?
A
They are all of nothing events and are all of the same amplitude (except from poison action)
6
Q
What are subthreshold depolarizations due to?
A
Upticks of depolarization due to a few voltage-gated Na+ channels opening but there is no response from the cell
7
Q
How fast does the cell depolarize once threshold is reached? How come?
A
Very fast due to + feedback: the opening of Na+ channels induces more channels to open
8
Q
What is the voltage of the resting membrane potential?
A
-70mV
9
Q
What is the threshold for the first ion channel to open?
A
-50mV
10
Q
What is the overshoot?
A
When the depolarization surpasses 0mV
11
Q
What is the reversal/equilibrium potential of Na+?
A
+60mV
12
Q
What regulates the Na+ channel to close? How does this affect permeabilities?
A
Time and voltage
- Na+ channels deactivate → decrease in GNa+
- V-gated K+ channels open → increase in GK+
13
Q
What happens when the Na+ channels reach equilibrium potential?
A
They close and the K+ channels open (delayed rectifier) = repolarization
14
Q
What is the undershoot? Why is it due to?
A
Membrane is hyperpolarized to a level below that of the RMP because the delayed rectifier K+ channels have a slower activation kinetics than the voltage-gated Na+ channels
15
Q
What regulates the K+ channel to close?
A
Hyperpolarization to slightly below -70mV
16
Q
What does poisonous fugu cause?
A
It poisons and irreversibly blocks Na+ channels with tetrodotoxin (TTX) = death because of respiratory failure
17
Q
Can the equilibrium voltage = the RPM?
A
Yes, if there is only one ion that can go through the membrane channels
18
Q
What is the convention to draw currents?
A
- Inward: drawn downward
- Outward: drawn upward
19
Q
What are non-poisonous, reversible blockers of Na+ channels?
A
Lidocaine, cocaine, anti-arrhythmic drugs
20
Q
What is the purpose of a voltage clamp experiment?
A
Voltage is held at a specific value and current is measured, which is basically measuring the membrane’s conductance which depend on their number of channels (permeability) for many different ion channels
21
Q
What is the purpose of a current clamp experiment?
A
Keep current constant and measure voltage
22
Q
What does poisining Na+ or K+ channels allow us to do?
A
Identify which channels are responsible for which parts of the action potential curve
23
Q
What does Tetraethylammonium (TEA) do?
A
Blocks voltage-gated K+ channels
24
Q
What do patch clamp experiments measure?
A
The activity of a single channel
25
Do all ion channels work similarly to the Na+ and K+ channels every time? How is this visible?
NOPE
Each channel displays a variety of open/closed channel patterns that can be visualized as an average curve that represents the global current resulting from the average behavior of each of the individual ion channels
26
Na+ channel:
* Activation speed?
* Number of conformations?
* Inward or outward current?
* Dependent on time and/or voltage?
* Fast activation/inactivation
* Open, closed, or inactive
* Begins outward and will reverse to inward near +60mV
* Dependent on both time and voltage
27
K+ channel:
* Activation speed?
* Number of conformations?
* Inward or outward current?
* Dependent on time and/or voltage?
* Slow activation
* Open or closed (do not inactivate as long as there is voltage)
* Outward current
* Dependent on voltage only
28
What is a genetic disorder associated with Na+ channels? What is it caused by? What is the result?
Hyperkalemic periodic paralasys or paramyotonia congenita: caused by several AA mutations which result in the disruption of the Na+ flow and muscle fatigue
29
What is the Na+ transmembrane domain 4 responsible for?
Voltage sensor of the Na+ channel
30
What part of the Na+ channel is the P-loop? What do mutations in this area cause?
Domain 5
Mutations ⇒ depolarization of RMP = epilepsy
31
What is the effect of Ca2+ on voltage-gated Na+ channels? How? Explain how it works.
It can shield their voltage sensors by altering what the sensor is reading:
* Excess extracellular Ca2+→ Lower perceived membrane potential → Decreased excitability ⇒ Threshold shifts to a more polarized value (more +)
* Shortage of extracellular Ca2+ → Larger perceived membrane potential → Increased excitability ⇒ Threshold shifts to a less polarized value (less +)
32
What is the absolute refractory period? What causes the absolute refractory period? When is this?
Time in which no action potential **CANNOT** be generated
Na+ channels are inactive and need to go back to closed state: when the axon is getting depolarized and hyperpolarized (bell of the curve) the cell is unable to fire another action potential
33
What is the relative refractory period? What causes the relative refractory period? When is this?
Time during which an action potential can be generated by a **STRONGER STIMULUS**
The need for the membrane to be repolarized back to RPM: from hyperpolarization to resting potential
34
What prevents the action potential from propagating in 2 directions?
Na+ channels being in the inactivated state after
35
What are 3 advantages of the voltage clamp compared to the current clamp?
1. When the membrane is changing the voltage, voltage-gated channels are going to screw up the voltage reading
2. Using current clamp you are bound by capacitance: the response to an injected current will be slowed by capacitance as capacitance steals current from the AP VS using voltage clamp you can bypass the capacitance completely
3. Voltage clamp experiments are more informative as they give data on the conductance changes over time
36
What types of muscles does the autonomic NS control?
Smooth muscles
37
What types of muscles does the somatic NS control?
Skeletal muscles
38
What type of clamp experiment do you use to determine which ion fluxes make up an action potential? Why?
Voltage clamps because if you use a current clamp, you will have no way of controlling the action potential when it starts
39
On what animal were axon potentials studied?
Squid
40
In the Na+/K+ pump, which current is positive and which one is negative?
* K+ current is NEGATIVE (going INSIDE)
* Na+ current is POSITIVE (going OUTSIDE)
41
What is the reverse potential for a particular ion?
The voltage at which it will go in the opposite direction
42
What is an experiment to determine what ions a particular membrane is permeable to?
Voltage clamp to find the reverse potential
43
Explain the patch clamp experiment.
Voltage clamp experiment is reproduced at the microscopic level of a single K+ or Na+ voltage-gated channel.
**FINDINGS:** single channel does not exhibit the same current graph as during the voltage clamp experiment. The graph of the voltage clamp experiment is a average result of numerous experiments on the same channel.
44
Does a single ion channel have a threshold? Why or why not?
NOPE because the threshold comes from the relationships between different ion channels
45
What are the 2 types of K+ channels involved in an action potential and what is the role of each?
1. Leakage K+ channels: at threshold the voltage-gated Na+ channels are at equilibrium with leakage K+ channels = critical number of voltage-gated Na+ channels opening to OVERCOME the K+ leakage channels
2. Voltage-gated K+ channels: responsible for repolarization of the cell
46
What does the membrane potential approach during the peak of the axonal action potential?
The Na+ equilibrium potential
47
Is the action potential duration associated with voltage-gated K+ channels? Why or why not?
Yes because the duration of the action potential depends on how quickly repolarization happens
48
What are the 4 key players for membrane repolarization?
1. K+ leakage channels
2. K+ voltage-gated channels
3. Inactivation of Na+ channels
4. Na+/K+ ATPase pump
49
What does the amplitude of the action potential depend on? Why?
Mainly dependent on the number of sodium voltage-gated channels because regardless of the electrochemical gradient, there is a limited amount of sodium that will be able to enter the cell before the potassium voltage-gated channels open.
If outside concentration is SIGNIFICANTLY reduced: amplitude will be lower though
The delay of K+ current activation can also have an impact.
50
What do we call the speed of propagation of the action potential? Units?
Conduction velocity (m/s)
51
What do conduction velocities depend on? 4 factors
The time and space constants:
1. Time constant = Rm . C
2. lambda = SR (Rm/Ri)
* Internal resistance (due to diameter of axon)
* Axon membrane capacitance (therefore myelation)
* Membrane resistance
* Activation kinetics of the Na+ channel
52
How does myelation affect a neuron?
Increase myelin =
* Increased conduction (because decreased time constant):
* Decreased capacitance, because increase distance between in and out of the cell → store less charges because attraction between inside and outside decreases so repulsive charges inside can't be too close b/c not as compensated for
* Increased membrane resistance (but overcome by decreased capacitance)
53
What determines how far a current will spread? What is the equation? What does this mean conceptually?
**Space constant = distance an AP can travel before it reaches 37% of its initial strength**
lambda = SR (Rm/Ri)
* Rm = membrane resistance
* Ri = internal resistance = 1/diameter of the cell
54
What types of cells generate myelin?
* CNS: Oligodendrocytes
* PNS: Schwann cells
55
What do we find at the nodes of Ranvier?
Na+ voltage-gated channels
56
What is the unidirectional movement of an action potential from the axon hillock to the nerve terminal due to?
**BOTH** refractory periods of the action potential
57
Is this RMP of most cells closer to the equilibrium potential of Na+ or K+? Why?
Closer to K+ because the membrane is more permeable to K+ (more K+ leakage channels than Na+ leakage channels)
58
Is the potential of the action potential at max depolarization of most cells closer to the equilibrium potential of Na+ or K+? Why?
Na+ because voltage-gated channels are open and permability of Na+ \> K+
59
What kind of feedback do we call the one involved once threshold is reached?
The current through the Na+ channels is self-sufficient to continue depolarization in a regenrative cascade of + feedback
60
What is the command potential?
The experimentally-set voltage in a voltage clamp experiment
61
What allows for depolarization spreading/propagation to the nearby membrane?
Local circuit currents produced by an action potential
62
What would a 50% drop in Ca2+ levels lead to?
Tetany (high rate of action potentials) in PNS which could result in paralysis of respiratory muscles and death
63
How does increasing the space constant affect the AP?
Increases the speed and distance it can travel
64
What can increase the space constant? 2 factors
1. Increase axon diameter = increase in internal resistance (ions can travel longer distances without colliding with an obstacle)
2. Increase membrane resistance = reducing the amount of current lost to the surroundings
65
What affects membrane resistance? 3 factors
* Properties of phospholipids
* Number of leakage channels
* Presence of myelin
66
What is an example of a disease resulting from demyelanation? Explain it.
MS: K+ channels are essentially absent in the nodes of Ranvier whereas they are highly concentrated in the myelin sections so demyelation will cause an increase in K+ permeability
67
How do we call the myelated and the demyelated sections on an axon?
* Myelated: paranodal axolemma
* Demyelated: nodal axolemma = nodes of Ranvier
68
When K+ blood concentration is low, how will this affect the action potential?
When the K+ blood concentration is low, the drive for the K+ ion to leave the cell is high, which means the membrane potential will reach even lower values during hyperpolarization = will need a higher stimulus for an action potential to happen = lower excitability
69
When K+ blood concentration is high, how will this affect the action potential?
The neuron will be more excitable because the resting membrane potential will be higher
70
What channel is responsible for returning the neuron to the RMP after the undershoot?
The Na+/K+-ATPase pump
71
When is the Na+/K+ ATP-ase pump working during an AP?
THE WHOLE TIME
72
What is the Na+/K+ permeability ratio during an AP?
10:1
73
How long does the absolute refractory period last?
1-2 ms
74
What happens if you inject current in the center of an axon?
APs will go in both directions
75
What is membrane resistance a factor of?
The number of channels in the membrane
76
Are there VG Na+ channels in the myelanated areas?
NOPE
77
How is the concentration of Na+/K+ ATPase channels at the nodes of Ranvier?
Very high!
78
How does the speed of an ion through a channel compare to that through a transporter?
Much faster through ion channels!
79
Is the curve of flux vs ion concentration linear?
NOPE
80
What is periodic paralysis due to?
Hyperkalemia: makes RMP more depolarized (makes it more positive), closer to threshold, hyperexcitable
BUT
This also causes inactivation of the voltage-gated sodium channels and periodic paralysis.
81
Why are Na+ time-dependent?
Because the speed of activation and recovery from inactivation are both dependent on time
82
What can make the peak of the AP smaller/larger?
83
What is the largest possible peak of the AP?
ENa = +60 mV
84
What are the 3 factors that can actually move the threshold?
1. Calcium through its shielding effect on Na+ VG channels
2. Number of K+ leakage channels
3. Number of Na+ VG channels
85
How do the conductance thresholds of Na+ and K+ voltage-gated channels compare to each other on the presynaptic cell in an AP?
Na+ and K+ voltage-gated channels have the same conductance threshold, but the K+ VG channels are delayed rectifiers so it takes them longer to open (allowing for the overshoot).
