Action Potential Flashcards

1
Q

Action potential components

A

)
* Overshoot (> 0 mV)
* Rising phase
* Threshold (all-or-none)
* Falling phase
Undershoot (below RMP)

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2
Q

An action potential is the result of

A

selective (voltage- and time-dependent) increases in the membrane’s permeability to Na+ and K+

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3
Q

Alan Hodgkin realized that to understand ion flux across the membrane…

A

it was necessary to eliminate differences in membrane potential.

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4
Q

In the 1940s Kenneth Cole and George Marmount had developed the
concept of

A

the voltage clamp.

Cole discovered that it was possible to use two electrodes and a feedback circuit to kp the cell’s membrane potential at a level set by the experimenter

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5
Q

The voltage clamp allows the

A

membrane voltage to be manipulated
independently of the ionic currents, allowing the current-voltage
relationships of membrane channels to be studied.

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6
Q

Hodgkin and Huxley used the voltage clamp to

A

outline the ionic
mechanisms that underlie the action potential (published 1952).
They received the Nobel Prize in Physiology or Medicine in 1963.

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7
Q

current flow aqccross the membrane was observed in

A

response to depolarization, but not hyperpolarization.

Effect is voltage dependent

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8
Q

direction of current flow is
defined as

A

net movement of
positive charge.

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9
Q

inward current

A

Flow of positive charge into
the cell (or negative charge
out of the cell)

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10
Q

In voltage-clamp experiments the flow of positive charge into the cell (the inward current) is typically shown as

A

a
downward deflection.

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11
Q

The reversal- (equilibrium) potential gives clue about the ionic nature of the early inward current:

A

The equilibrium potential is the
potential at which the electrical force offsets the movement of an ion due to its concentration gradient → no
net current flows

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12
Q

Action potential depolarization/amplitude
depends

A

greatly on Na+ gradient (but the resting potential does not)

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13
Q

depolarization of the membrane has 2 effects:

A
  • an early influx of Na+
    into the neuron, (produces transient/inactivating inward current)
  • followed by a delayed efflux of K+ (produces non-inactivating outward current)
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14
Q

The current through each class of voltage-gated channel can be calculated from

A

Ohm’s law

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15
Q

Calculating conductances of an active channel population

A
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16
Q

total ionic current as the sum of separate Na+
, K+
, and leak currents:

Hodgkin and Huxley

A

predictions for the probability of channels being open.

m and h (for activation and inactivation of gNa) or n (for activation of gK ) M, n (and h) describe the probability of “particles” to be in the correct position to open (or to inactivate, respectively) a channel.
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17
Q

Calculation of Membrane Conductances From Voltage-Clamp Data

m

A

activation of gNa

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18
Q

Calculation of Membrane Conductances From Voltage-Clamp Data

n

A

inactivation of gNa

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19
Q

Calculation of Membrane Conductances From Voltage-Clamp Data

h

A

activation of gK

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20
Q

Membrane conductance

A

(g)

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21
Q

Vm

A

(resting potential)

controlled through the voltage clamp

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22
Q

I(ion)

A

measured by isolating the current in
ion-substitution experiments (or through
pharmacological blockade)

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23
Q

(Vm – Eion)

A

the electrochemical driving force

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24
Q

M, n (and h) describe

A

the probability of “particles” to be in the correct position to open (or to inactivate, respectively)
a channel.

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25
Q

Ƭ (tau)

A

time constant of change

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26
Q

“delayed rectifier”.

A

require time to turn on, but K+ much slower, requiring several ms to reach its peak

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27
Q

The Na+ channels must inactivate, because

A

the
current goes off even when it is depolarized.

28
Q

The K+ channels…

A

do not inactivate - if the cell is
depolarized, they are open.

29
Q

Refractory period

A
  • gNa+ inactivated
  • gK+ activated over Rest (→ undershoot)
30
Q

Absolute refractory period

A

a second AP can not be initiated, under no circumstances

31
Q

Relative refractory period

A

initiation of a second AP is inhibited but not impossible.

32
Q

Properties of Na+ and K+ channels that underlie the shape of the AP

A

Show ion selectivity
* Both are voltage-gated
* Have voltage-sensor
→ depolarization increases open probability,
while hyperpolarization closes them.
* Na+ channel has mechanism for inactivation

33
Q

The AP threshold is reached, when

A

the Na+ conductance (the inward current) outweighs the opposing
force of the K+ conductance (outward current).

34
Q

Threshold of Na+ channels

A

Na+ channels have no threshold.
Instead, they open in response to depolarization in a stochastic manner.

35
Q

Depolarization does not

A

so much open the channel
as it increases the probability of it being open.

36
Q

Green Arrow is

A

the resting potential of
the cell.

As the K+ channel is virtually the only one
open at these negative voltages, the cell will rest very
near to the equilibrium potential for potassium Ek
.

37
Q

Yellow Arrow is…

A

the equilibrium potential
for Na+
(ENa).

In this two-ion system, ENa is the
natural limit of membrane potential beyond which a cell cannot pass.
Current values illustrated in this graph that exceed ENa are measured by artificially pushing the cell’s voltage past its natural limit.
However, ENa could only be reached if the opposing
potassium current was absent.

38
Q

Blue Arrow is…

A

the maximum voltage that the peak of the action potential can approach.

his is the
actual natural maximum membrane potential that this cell can reach.
It cannot reach ENa because of the counteracting influence of the potassium current.

39
Q

Red arrow is…

A

the action potential threshold.

This is where I
sum becomes net-inward.
Note that this is a zero-current crossing, but with a negative slope.
Any such “negative slope crossing” of the
zero current level in an I/V plot is an unstable point.
At any voltage negative to this crossing, the current is outward and so a cell will tend to return to its resting potential.
At any voltage positive of this crossing, the current is inward and will tend to depolarize the cell.
This depolarization leads to more inward current, thus the
sodium current becomes regenerative.
The point at which the green line reaches its most negative value is the point where all sodium channels are open. Depolarizations beyond that point thus decrease the sodium current as the driving force decreases as the membrane potential approaches ENa.

40
Q

Identity of information (e.g. sensory input) is

A

based on wiring

41
Q

Intensity is

A

based on frequency

42
Q

Calcium-currents during APs

A

depolarizes the cell (inward current)
* Opens Ca++-activated K+ channels (IKCa) .
* Inactivates Ca++ channels that are themselves sensitive to levels of intracellular Ca++ and are inactivated when incoming Ca++ binds to their intracellular surface.
* Activates a Ca++
-sensitive protein phosphatase, calcineurin, which dephosphorylates (inactivates) voltage gated Ca++ channels

43
Q

Ca++ influx during an action potential can have two opposing effects:

A
  1. The positive charge that Ca++ carries into the cell contributes to the regenerative depolarization, while
  2. the increase in cytoplasmic Ca++ results in the opening of more K+ channels and the closing of Ca++ channels,
    causing repolarization.

Ca++ channels underlie depolarizing
“hump”

44
Q

Many neurons have 2 firing modes:

A

“Regular” firing and burst firing

Hyperpolarization can cause Ca++
channels to recover from inactivation

45
Q

The effect of ion channels on the firing pattern depends
on

A

their dendritic location

46
Q

Blocking Ca++ channels with
cadmium

A

transforms bursts into
regular action potentials

47
Q

Injection of current at the dendrites induces

A

Ca++ potentials at P2 and burst firing
at the soma (P1).

48
Q

Current Injection at the soma

A

only induces
regular firing (P1 and P2)

49
Q

Propagation of the action potential is

A

not unidirectional

50
Q

At low stimulus intensities, AP initiation occurs

A

in the AIS,
followed by propagation back into the dendrites (bAP).

51
Q

At higher stimulus intensities

A

localized dendritic spikes
can precede AP initiation in the axon.

52
Q

Dendritic spikes with relatively narrow widths (<5
ms) are

A

are usually mediated by Nav channels
(“dendritic sodium spikes”).

As with all dendritic
spikes, dendritic sodium spikes can occur in the
absence of axonal action potentials and are
therefore distinct from backpropagating APs.

53
Q

A second type of dendritic spike, which is broader
(>10 ms) and usually evoked by more prolonged
dendritic depolarization, is

A

mediated primarily by
Cav channels (dendritic calcium spikes).

54
Q

A third type of dendritic spike is mediated primarily
by

A

NMDA receptors (NMDA spike).

These events
can be even longer in duration and tend to be
initiated in small-diameter dendritic branches such
as basal and tuft dendrites of pyramidal neurons.

55
Q

The electrical properties of the axon initial segment (AIS) determine

A

the precise timing of the APs in
response to fluctuating synaptic inputs

56
Q

The AIS plays an important role in
maintaining neuronal polarity by

A

regulating the trafficking and
distribution of proteins that function
in somatodendritic or axonal
compartments of the neuron.

57
Q

Adaptive changes to the location and
length of the AIS can

A

fine-tune the
excitability of neurons and modulate
plasticity in response to activity.

58
Q

The dense protein clustering in the AIS
serves as a

A

selective diffusion barrier,
maintaining the distinct composition
between the somatodendritic and axonal
plasma membrane.

59
Q

Potassium channels contribute to

A

afterhyperpolarizations

  • slow AHP → unknown
60
Q

fast AHP

A

BK channels

61
Q

Medium AHP

A

SK channels
Kv7 channels

62
Q

slow AHP

A

unknown

63
Q

Afterdepolarization

A

T-type, R-type Ca2+ channels; persistent Na+ channels (INaP)

64
Q

The pattern of action potential firing is modulated by

A

neurotransmitters

65
Q

Hyperpolarization-activated cation (HCN) channel or Ih

A

activated by hyperpolarization
* closes at positive potentials
* gates very slowly
blocked by cesium (or ZD 7288)
* almost as permeable to Na+ as to K
HCN channels pass an inward current
Initiates slow depolarization when the membrane has become very negative

66
Q

Ih
contributes to

A

pacemaking (thalamus, heart)