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Action Potentials

Anatomy and Physiology


Learning Objectives
• Introduce nerve impulse transmission
• Describe and explain transmembrane potential
• Understand the processes involved in an action
potential
Transmembrane Potential

• Ion Movements and Electrical Signals


• All plasma (cell) membranes produce electrical signals
by ion movements
• Transmembrane potential is particularly important to
neurons

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Nerve Impulse Transmission
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Extracellular

+ + + + + + + + + +
– – – – – – – – – –


– – – – – – – – – –

+ + + + + + + + + + –

-- – –
Electrode -- +40 mV Electrode –
outside axon -- inside axon Intracellular –
-- –0 mV –
-- Oscilloscope
-- proteins and nucleic acids
screen
–70 mV K+
Na+

4
Transmembrane Potential
• Membrane Processes in Neural Activities
• Resting potential
• The transmembrane potential of resting cell

• Graded potential
• Temporary, localized change in resting potential

• Caused by even a weak stimulus

• Action potential
• A rapid change in membrane potential which is transmitted

• Caused by a strong stimulus

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Membrane
Potential
Transmembrane Potential
• Passive Forces Acting Across the Membrane
• Chemical gradients
• Concentration gradients of ions (Na+, K+)

• Electrical gradients
• Separate charges of positive and negative ions

• Result in potential difference

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Transmembrane Potential
• Equilibrium Potential
• The transmembrane potential at which there is no net
movement of a particular ion across the cell membrane
• Examples
K+ = –90 mV

Na+ = +66 mV

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Cummings
Transmembrane Potential
• Active Forces Across the Membrane
• Sodium–potassium ATPase (exchange pump)
• Is powered by ATP

• Carries 3 Na+ out and 2 K+ in

• Balances passive forces of diffusion

• Maintains resting potential (–70 mV)

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Cummings
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Resting membrane potential

• At rest, the plasma membrane is highly permeable to


potassium ions (they move out)
• Membrane is almost impermeable to sodium ions
• Passive ion movement and the Na+/K+ pump create a
resting membrane potential
• Resting membrane potentials vary across cell types
• Neuron RMP = – 70 mV

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Transmembrane Potential

Figure 12–9 An Introduction to the Resting Potential.

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Nerve Impulse Transmission
• Graded potentials
• Small transient changes in membrane potential due to
activation of gated ion channels
• Each gated channel is selective to certain ion
• Most are closed in the normal resting cell

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Transmembrane Potential
• Three Classes of Gated Channels
• Chemically gated channels
• Open in presence of specific chemicals (e.g., ACh) at a binding site
• Found on neuron cell body and dendrites
• Voltage-gated channels
• Respond to changes in transmembrane potential
• Have activation gates (opens) and inactivation gates (closes)
• Characteristic of excitable membrane
• Found in neural axons, skeletal muscle sarcolemma, cardiac muscle
• Mechanically gated channels
• Respond to membrane distortion
• Found in sensory receptors (touch, pressure, vibration)

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Nerve Impulse Transmission
• Chemically-gated or Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

ligand-gated channels Na+


Synaptic cleft

• Ligands are hormones or Na


+
Na+
Acetylcholine
neurotransmitters
• Induce opening and cause
changes in cell membrane
permeability Cell
membrane

Receptor Na+
protein
Ion Na+
channel

Cytoplasm in postsynaptic cell

15
Action potential
• Depolarization makes the membrane potential
more positive
• Hyperpolarization makes it more negative
• These small changes result in graded potentials
• Size depends on either the strength of the stimulus
or the amount of ligand available to bind with their
receptors
• Summation is the ability of graded potentials to
combine

16
Action potential
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1 E1 2 E2 3 I 4 E 1+E2+I
–68
Membrane potential (mv)

–69

–70

–71

–72

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Action potential
• An action potential has three phases
1. Rising (depolarisation)
2. falling (repolarisation)
3. undershoot (hyperpolarisation)
• Intensity of a stimulus is coded by the frequency,
not amplitude, of action potentials

18
19
Voltage-Gated
Na & K
+ +

Channels

20
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2. Rising Phase 3. T op of Curve

Stimulus causes above threshold voltage Maximum voltage reached

Potassium
gate opens

K
K++
Na
Na+
Na+ channel
Sodium channel inactivation gate
activation gate opens closes

Membrane potential (mV)


+50

–70

1. Resting Phase 1 2 3 4. Falling Phase


Time (ms)
Equilibrium between diffusion of K+ out Undershoot occurs as excess potassium
of cell and voltage pulling K+ into cell diffuses out before potassium channel closes

Potassium
Voltage-gated Potassium channel gate open
potassium channel gate closes

Equilibrium
restored

Potassium Na+ channel


Voltage-gated Sodium channel
channel inactivation gate
sodium channel activation gate closes. closed
Inactivation gate opens.
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Action potential
• Action potentials
• Result when depolarization reaches the threshold
potential (–55 mV)
• Depolarizations bring a neuron closer to the threshold
• Caused by voltage-gated ion channels
• Voltage-gated Na+ channels
• Voltage-gated K+ channels

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Action Potential

• Initiating Action Potential


• Initial stimulus/depolarisation
• A graded depolarization of axon hillock large enough (10 to 15
mV) to change resting potential

(-70 mV) to threshold level of voltage-gated sodium channels


(–60 to –55 mV)

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Action Potential
• Initiating Action Potential
• All-or-none principle
• If a stimulus exceeds threshold amount:
• the action potential is the same

• no matter how large the stimulus

• Action potential is either triggered, or not

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Cummings
Action Potential
Depolarization
• A shift in transmembrane potential toward
0 mV:
• movement of Na+ through channel
• produces local current
• depolarizes nearby plasma membrane (graded potential)
• change in potential is proportional to stimulus

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Cummings
Action potential
• Repolarization
• When the stimulus is removed, transmembrane potential returns
to normal
• Hyperpolarization
• Increasing the negativity of the resting potential
• Result of opening a potassium channel
• Opposite effect of opening a sodium channel
• Positive ions move out, not into cell

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Cummings
Transmembrane Potential

Figure 12–13 Depolarization, Repolarization, and Hyperpolarization.


Copyright © 2009 Pearson Education,
Inc., publishing as Pearson Benjamin
Cummings
Action Potential
• Generation of Action Potentials
• Step 1: Depolarization to threshold
The Generation of an Action
• Step 2: Activation of Na channels
+ Potential (Step 1).

• Rapid depolarization

• Na+ ions rush into cytoplasm

• Inner membrane changes from


negative to positive

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Cummings
Action Potential
• Generation of Action Potentials
• Step 3: Inactivation of Na+ channels,
activation of K+ channels
• At +30 mV
The Generation of an Action
• Inactivation gates close (Na+ channel inactivation)
Potential (Step 3).

• K+ channels open

• Repolarization begins

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Cummings
Action Potential
• Generation of Action Potentials
• Step 4: Return to normal permeability
• K+ channels begin to close:
• when membrane reaches normal resting
The Generation of an Action
potential (–70 mV)
Potential (Step 4).
• K+ channels finish closing:
• membrane is hyperpolarized to -90 mV
• transmembrane potential returns to
resting level:
• action potential is over

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Inc., publishing as Pearson Benjamin
Cummings
• The Refractory Period
• The time period
• From beginning of action potential
• To return to resting state
• During which membrane will not respond normally to additional stimuli
• Absolute refractory period
• Sodium channels open or inactivated
• No action potential possible
• Relative refractory period
• Membrane potential almost normal
• Very large stimulus can initiate action potential

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Cummings
Refractory
Period

32
Action Potential

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Cummings
Mechanism of
an Action
Potential

34
Nerve Impulse Transmission
• Propagation of action potentials
• Each action potential, in its rising phase, reflects a reversal
in membrane polarity
• Positive charges due to influx of Na+ can depolarize the
adjacent region to threshold
• And so the next region produces its own action potential
• Meanwhile, the previous region repolarizes back to the
resting membrane potential
• Signal does not go back toward cell body

35
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resting
repolarized
depolarized

+ + + + + + + + + +
– – – – – – – – – –
Cytoplasm
Cell + – – – – – – – – – –
membrane + + + + + + + + +

– – + + + + + + + +
+ + – – – – – – – –
Na+
+ + – – – – – – – –
– – + + + + + + + +

K+
+ + – – + + + + + +
– – + + – – – – – –
Na+
– – + + – – – – – –
+ + – – + + + + + +
K+

K+
+ + + + – – – + + +
– – – – + + + – – –
Na+
– – – – + + + – – –
+ + + + – – – + + +
K+

K+
+ + + + + + + + – –
– – – – – – – – + +
Na+
– – – – – – – – + +
+ + + + + + + + – – 36
K+
Transmembrane Potential

Figure 12–12 Graded Potentials (Resting State).


Copyright © 2009 Pearson Education,
Inc., publishing as Pearson Benjamin
Cummings
Transmembrane Potential

Figure 12–12 Graded Potentials (Step 1).

Copyright © 2009 Pearson Education,


Inc., publishing as Pearson Benjamin
Cummings
Transmembrane Potential

Figure 12–12 Graded Potentials (Step 2).

Copyright © 2009 Pearson Education,


Inc., publishing as Pearson Benjamin
Cummings
Action Potential

Figure 12–15 Continuous Propagation of an Action Potential along an


Unmyelinated Axon (Steps 1 and 2).
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Inc., publishing as Pearson Benjamin
Cummings
Action Potential

Figure 12–16 Saltatory Propagation along a Myelinated Axon (Steps 1 and


2).
Copyright © 2009 Pearson Education,
Inc., publishing as Pearson Benjamin
Cummings
Action Potential

Figure 12–16 Saltatory Propagation along a Myelinated Axon (Steps 3 and 4).

Copyright © 2009 Pearson Education,


Inc., publishing as Pearson Benjamin
Cummings
Possible pathologies
• Neurotransmitter imbalances
• Depression – decreased serotonin

• Schizophrenia – astrocyte function impaired, increased dopamine,


hyperexcitability (GABAR upregulation, NMDAR hypofunction)
• Bipolar disorder – increased dopamine, excitotoxicity (glutamate)

• Anxiety – decreased serotonin and decreased GABA transmission

• Stress – continuous activation of the sympathetic NS, hormonal


release and neurotransmission.
• The Integrated Nervous System by Walter
Hendelman, M.D. Edition: 1st
• Introduction to anatomy and Physiology by Donald
C. Rizzo . Edition: 1st
• Human Physiology by Bryan Derrickson
• Human Physiology by Stuart Ira Fox. Edition: 13th

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