Action Potentials Flashcards
1
Q
Open when membrane is depolarized, slow inactivation, depolarizes after AP
A
Delayed rectifier K channel
2
Q
Where is the selectivity filter of the VG Na channel?
A
The loop between subunits 5 and 6
3
Q
What initiates closure of the inactivation gate in VG Na channels?
A
Outward movement of S4 (voltage sensor)
4
Q
Many properties displayed by the AP are due to properties of this channel
A
VG Na channel
5
Q
How does water play an important role in determining selectivity of the VG Na channel pore?
A
The size of a partially hydrated Na ion can fit but a partially hydrated K ion cant
6
Q
What are used to record APs?
A
Intracellular and extracellular electrodes
7
Q
What happens in the rising phase?
A
Na going into the cell, high Na conductance (how easy it is for ions to move), inside becoming positive
8
Q
From puffer fish, block VG Na channel
A
Tetrodotoxin
9
Q
What happens in the falling phase?
A
ABSOLUTE REFRACTORY. Na channels close and won’t open, K channels open, high K conductance
10
Q
Sea anemone toxins are active here
A
Site 3
11
Q
When the AP looks like it is jumping from noble to node
A
Saltatory conduction
12
Q
Channel with selective ion conductance for Na
A
VG Na channel
13
Q
When AP conduction is started from the end and moves toward cell body (rare)
A
Antidromic
14
Q
Are the a helical segments of the VG Na channel
A
S1-S6
15
Q
These two things help convey info about the neuron ion channels
A
Rate and pattern of firing
16
Q
Set by K channels
A
Relative refractory period
17
Q
These two VG channels structures are related
A
VG K and VG Na channels
18
Q
Why cant an AP be faster than 1 ms?
A
The absolute refractory period
19
Q
When do toxins have an effect on the VG Na channel?
A
When there is an AP. No effect if it is at rest
20
Q
Opening the inactivation gate is also tied to doing what with it?
A
Closing it
21
Q
What is deinactivation of the inactivation gate and when does it occur?
A
It is when the VG Na channel is not activated and the ball and chain falls out. It happens around -65 mV
22
Q
Tetrodotoxin and saxitoxin are active here
A
Site 1
23
Q
The voltage sensor of the VG Na channel that moves outward when the cell depolarizes
A
S4
24
Q
What does tetraethyl-ammonium do to cells?
A
Blocks K current outward
25
What happens to channels behind the AP that the AP has already passed?
They are refractory bc Na channels are inactivated
26
When AP conduction is started from the cell body
Orthodromic
27
Block pore and selectivity filter, specific amino acids required
Tetrodotoxin and saxitoxin
28
What is length constant?
How far current flows before it leaks out, before it is reduced to 37%
29
Used to deduce the nature of the AP
Voltage clamp and squid giant axon
30
Segment of VG Na channels that mostly line the pore
S6
31
These don't open right after depolarization, they are delayed
VG K channels
32
Composed of 4 subunits, each similar to one domain of the VG Na channel
VG K channels
33
Axon placed in saline solution, reference electrode in solution, electrodes hooked up to ultimately measure current at specific voltages
Voltage clamp
34
From a dinoflagellate, occurs in calms, shellfish, and mussels. Block VG Na channel
Saxitoxin
35
Na channels inactivated, cant be deainactivated until Vm is more negative
Absolute refractory period
36
This gate is less accessible after depolarization in the VG Na channel
Inactivation gate
37
What does I ion = g ion represent?
Current of the ion = conductance of the ion (Like Ohms law Vm - Eion)
38
What is needed to initiate an AP?
Depolarization of membrane due to generator potentials beyond some threshold (around -40 mV)
39
What are spike initiation zones?
In unmyelinated neurons, they are areas of high Na channel concentration
40
Part of the VG Na channel sensitive to proteases and antibodies
Inactivation gate
41
Used voltage clamp to determine ionic permeability changes during the AP
Hodgkin and Huxley
42
VG Na channels contain 4 of these
Four homologous domains
43
What is the maximum rate of an AP?
1000 Hz = 1 ms
44
Na channels inactivate, K channels open, large driving force for K to leave cell
Falling phase
45
Toxins that affect channel inactivation
Scorpion and sea anemone toxins
46
Techniques used to record electrical activity from single neurons or single channels
Patch clamp techniques
47
What are membrane conductance changes dependent on?
Time and voltage
48
Set by Na channels
Absolute refractory period
49
How does depolarization occur as the AP moves down the axon?
Successive patches of membrane are depolarized
50
These segments of VG Na channels move in specialized channels
S4
51
These areas contain many VG Na channels
Nodes of Ranvier
52
Mechanistic models of this channel were developed in the 1960s and 1970s
VG Na channels
53
These studies support S4 as voltage sensor because cysteine mutations showed outward movement
Mutagenesis studies
54
AP conduction moves down the cell in how many directions?
One direction
55
Sigma conotoxins are active here
Site 6
56
What happens to the concentrations of Na and K inside and outside the cell during an AP?
The relative concentrations stay the same even though Na flows in and K will flow out. K still higher in and Na still higher out
57
What does lidocaine do in the VG Na channel?
Blocks the inside channel (S6 segment)
58
This was used to examine the biophysical properties of individual Na channels
Patch clamp technique
59
What are generator potentials also known as and what do they do?
EPSPs. Bring the cell to threshold (-40 mV)
60
What are total Na and K currents composed of?
The sum of individual currents
61
What does the undershoot represent?
Relative refractory
62
How does the voltage sensor (S4) fit in each domain?
Slides within a channel in each domain
63
From frog, channels open at more negative voltages, stay open too long
Batrachotoxin
64
Vm (membrane potential) moves towards EK (eq pot for K), hyperpolarizing cel, little permeability to Na, opening of Ca activated K channels
Undershoot
65
Segments of VG Na channel that form inner pore
S6
66
SLIDES 14-18 GRAPHS
SLIDES 14-18 GRAPHS
67
What allows the cell to depolarize?
The faster opening of Na channels than K channels so K cant dominate and the cell becomes positive
68
What does myelin reduce?
Membrane capacitance
69
The falling phase of APs is also due to the opening of these, not just the closing of Na channels
Opening of K channels
70
Maintained by Na-K-ATPase
Gradients
71
An important type of K channels in APs and hyperpolarization
Delayed rectifier channels
72
Used to see what current is flowing at specific voltages
Voltage clamp
73
Many types of these, 80 subunit genes, multiple families
K channels
74
Are a brief reversal of charge (not gradients) in which the inside becomes briefly more positive than the outside
AP
75
What makes up the VG Na channel?
One protein with 4 domains that make it look like 4 proteins, this is the alpha subunit and there are B1 and B2 subunits on the ends
76
Also known as spike, discharge, nerve impulse
APs
77
What is the goal of an AP?
Ultimately stimulate the release of NTs
78
Is a wave of positive charge transmitted down the neuron
AP
79
Vm hyperpolarized until K channels close
Relative refractory period
80
The time when more current is required to fire AP
Relative refractory period
81
Local anesthetics block in these segments of the VG Na channel
S6
82
How does myelin help propagation?
Increasing length constant (how far current flows before it leaks out - reduced to 37%)
83
Frequency and pattern of these encode info
APs
84
AP conduction is propagated without doing what?
Decreasing strength
85
Used to look at the electrical activity of one channel
Patch clamp technique
86
Due to outward K current
Falling phase
87
Channel with two gates, including an inactivation gate that closes after about 1 ms and only opens when the cell returns to a more negative voltage
VG Na channels
88
What is required for fast inactivation in the VG Na channel?
3 key amino acids
89
What does an extracellular electrode oscilloscope display?
A dip to more negative (Na in), then a spike to above the resting to be a little positive (K out with overshoot), and then back to resting (different than normal AP curve)
90
Toxins used to isolate a, B1, and B2 subunits in mammalian brain, a and B1 in skeletal muscle, eel a in this channel
VG Na channels
91
These are used to study the function and structure of the VG Na channel
Toxins
92
What does the amount of depolarization control?
The firing frequency. More depolarization = more APs (all are always the same size)
93
What does tetrodotoxin do to cells?
Block Na current inward
94
Channel with rapid inactivation (open 1 ms)
VG Na channel
95
All chemical transmission depends on these
APs
96
What happens 1 ms after Na channels open in the AP?
Na channels close and the K channels open causing the cell to rapidly hyperpolarize
97
What is conductance?
How easy it is for ions to move
98
Vm (membrane potential) approaches ENa (eq pot for Na) greater than 0 mV
Overshoot
99
What does the inactivation gate form with the gate receptor in the VG Na channel?
It forms a hydrophobic interaction with it
100
Why was the squid axon used to study APs?
It is 800 um in diameter compared to humans 2 um. Easy enough to see and manipulate
101
What are AP firing patterns due to?
Type/combination of ion channels present
102
Why cant the membrane depolarize the area before an AP it just passed over?
It is in the absolute refractory period
103
Reentrant loop forms pore here in the VG Na channel
Between 5 and 6 of each domain
104
How does the inactivation gate of the VG Na channel work?
Closes after 1 ms and only opens when the cell returns to a more negative voltage
105
Na ions enter cell due to large driving force
Rising phase
106
What does an intracellular electrode oscilloscope display?
A spike up to a positive charge and a fall back down to negative with a little undershoot (Na in, K out, normal looking AP curve)
107
What are the B subunits required for in the VG Na channels?
Required for normal kinetics and voltage dependence of gating
108
Channel with voltage dependent activation (around -40 mV)
VG Na channel
109
Biochemical approaches led to the discovery of the proteins that make up this channel in 1980
VG Na channels
110
Caused by influx of Na ions through VG Na channels open for about 1 ms
Depolarization
111
Vm (membrane potential) at which Na channels open, more permeable to Na
Threshold
112
At what voltage does the VG Na channel open?
-40 mV
113
Caused by efflux of K ions through VG K, brings cell back to -65 mV
Repolarization
114
Produced by entry of positive charges into the cell
Generator potential (small changes in voltage)
115
Contain immunoglobulin like folds (look like antibodies) in VG Na channel
B1 and B2
116
What are intracellular and extracellular recordings measured in?
```
Intra = mV
Extra = uV
```
117
Brevetoxins and ciguatoxins are active here
Site 5
118
What does a more excited cell have in terms of APs?
More APs, more frequency, not bigger APs
119
Due to inward Na current
Rising phase
