Chapter 12

Nerve Impulses

Alex Foxworthy, PhD

ESCC
Neurotransmission: Introduction
• http://www.viddler.com/embed/f9be82ab

Nerve Impulse
• http://www.viddler.com/embed/c61fdef6
 Pumps and Channels
• Pumps
– Require ATP
– Move substance against concentration gradient
• Channels
– No ATP
– Move substance down concentration gradient
– Types
• Chemically gated channels
• Voltage-gated channels
• Mechanically gated channel
 • Pumps
– Type of transport protein
– Move substances against concentration gradient
– Require energy
• e.g., sodium-potassium and calcium pumps in plasma membrane
(Figure 12.10a)

Interstitial Cytosol
fluid Breakdown of ATP
(releases energy)
K+
K+ ATP binding
site

ATP ADP
P
Na+
Na+
Na+/K+ pump changes
Na+/K+ shape (requires energy
pump from ATP breakdown)

(a) Sodium-potassium (Na+/K+) pump

 Chemically Gated Channels
• Channels The ACh receptor
we saw at the NMJ
– Chemically gated channels is an example
• normally closed; open when neurotransmitter binds
• allow specific type of ion to diffuse when open
• e.g., chemically gated K+ channels

Closed Open

Neurotransmitter
binds to gate

K+

(c) Chemically gated channels

 • Channels Chemically Gated Channels
– Voltage-gated channels
• normally closed
• open in response to change in electrical charge across membrane
• allow specific type of ion to diffuse
• e.g., voltage gated Na+ channels

Closed (resting state) Open (activation state)

+ + + + + + + + – – – – – – – –

– – – – – – – + + + + + + +
Inactivation Inactivation
gate (open) Activation gate (open) Activation
Na+ gate (closed) Na+ gate (open)
(d) Voltage-gated channels (three different states)
 Distribution of Pumps and Channels
Distribution of pumps and channels
• Entire plasma membrane of neuron
– Na+/K+ pumps
– important in maintaining resting membrane potential
 Distribution of Pumps and Channels
Membrane of functional segments in a neuron
1. Receptive segment
• includes dendrites and cell body
• chemically gated channels here (cation channels, K+, Cl-)
• no significant voltage-gated channels
2. Initial segment
• composed of axon hillock
• contains voltage-gated Na+ and K+ channels
3. Conductive segment
• length of the axon and its branches
• contains voltage-gated Na+ and K+ channels
4. Transmissive segment
• includes synaptic knobs
• contains voltage-gated Ca2+ channels and pumps
 Plasma membrane of entire neuron

Receptive segment
Chemically Chemically Chemically
gated cation gated K+ gated Cl–
channel channel channel

(b)
Cell body

Distribution Dendrites

Axon hillock
Initial segment
Voltage-gated Voltage-gated
Na+ channel K+ channel

of Pumps and Na+/K+ Na+ leak K+ leak (c)

Channels in pump channel channel

Conductive segment
Voltage-gated Voltage-gated
+
Na channel K+ channel

the Plasma Entire neuron

Membrane of Axon

a Neuron

(d)

Transmissive segment
Voltage-gated Ca2+ pump
Ca2+ channel

(a) Synaptic bulb

(e)
 Ultrastructure of Neurons:
Pumps and Channels
What is the difference between a chemically
gated channel and a voltage-gated channel
in terms of how they function?
 Distribution of Substances and Membrane
Potentials

• Distribution of substances inside and outside neuron

• The inside is negative (~ -70mV) compared to the outside

• This distribution is maintained by the Na+/K+ pump

Na+ Cl- Ca2+

K+ Protein-
 Neuron at Rest – see the distribution of
channels at the receptive, initial, conductive
and transmissive segments

Figure 12.13a
12
 Changing the Membrane Potential

• Depolarization and hyperpolarization

– Opening of chemically gated channels or voltage-gated channels
– Causes change in ion flow across membrane
– Alters resting membrane potential
– Depolarization
• inside of cell becomes more positive than RMP
• e.g., from -70 mV to -60 mV
• occurs when gated channels open
• movement of Na+ into neuron
• causes inside of neuron to become more positive
 Changing the Membrane Potential

• Depolarization and hyperpolarization (continued)

– Hyperpolarization
• inside of cell becomes more negative
• e.g., from -70 mV to -80 mV
• may result from opening of gated K+ channels
• may result from opening of gated Cl- channels
• loss of positive ion (K+) or gain of negatively charged ion (Cl-)
Changing the Resting Membrane Potential: Resting
Membrane Potential

–70 mV

+ ++ +++++++
– –– ––––– ––
– –– ––––– ––
+ ++ +++++++
Gated Na+ Gated K+ Gated Cl–
channel channel channel

Na+
Interstitial Cl–
fluid
+ + + + + + + + + + + + + +
Plasma
membrane
– – – – – – – – – – – – – –

Cytosol
K+ e.g., –70 mV

(a) Resting membrane potential

Changing the Resting Membrane Potential:
Depolarization

–60 mV

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

Gated Na+ channel

Cl–

+ + + + + + + + + + + + +

– – – – – – – – – – – – – – –

Na+
K+
e.g., –60 mV

(b) Depolarization: Na+ flows in

Changing the Resting Membrane Potential:
Hyperpolarization

–80 mV

+ + + + + ++ + + +
– – – – –– ––– –
– – – – –– ––– –
+ + + + + ++ + + +
Gated K+ Gated Cl–
channel channel

Na+ K+
Cl–

+ + + + + + + + + + + + +

– – – – – – – – – – – – –

e.g., –80 mV

(c) Hyperpolarization: K+ flows out or Cl– flows in

 Receptive Segment
• Reception of neurotransmitter triggers postsynaptic potential
– Neurotransmitter binds to chemically gated ion channels and opens them
– Ions diffuse across membrane changing its electrical potential
– graded potential is triggered
• can vary in size (from a few mV to many mV)
• a local potential: (starts at dendrites or soma and does not go far)
• Short lived
– The direction of the potential depends on what type of ion channel opens
• If Na+ channels open, Na+ diffuses in and membrane becomes less negative
• If Cl– channels open, Cl– diffuses in and membrane becomes more negative
• If K+ channels open, K+ diffuses out and membrane becomes more negative

18
 Receptive Segment: Graded Potentials

• Graded potentials
– Local potentials
– Depolarizing or hyperpolarizing
– Can be strong or weak depending on strength of stimulus
– Short lived
– Strength decreases with time and distance
– Location
• Dendrites
• Cell body
– Due to opening of chemically gated channels
– Temporarily allow passage of small amount of specific ion
 Receptive Segment: EPSP

Generation of EPSPs (excitatory post synaptic potential)

• Sequence of events
1) Excitatory neurotransmitter crosses synaptic cleft.
• binds to receptor
• opens a chemically gated cation channel
2) More Na+ moves into neuron than K+ moves out.
3) Inside becomes slightly more positive.
• excitatory postsynaptic potential (EPSP)
4) Local current of Na+ becomes weaker
• decreases in intensity with distance traveled

– Degree of change in RMP

• dependent on amount of neurotransmitter bound per unit time
– More excitatory neurotransmitter released
• more cation channels open
• greater change in the positive direction
• e.g., from -70 mV to -65 mV
 Receptive Segment: Postsynaptic Potentials
Excitatory postsynaptic potentials (EPSPs) are depolarizations
caused by cation entry

Figure 12.15a 21
 Receptive Segment: IPSP

Generation of IPSPs (inhibitory post synaptic potential)

• Sequence of events
1) Inhibitory neurotransmitter crosses synaptic cleft.
• binds to chemically gated K+ channel or Cl- channel
• depends on neurotransmitter and channels present
2) If neurotransmitter binds K+ channel, K+ moves out of neuron.
If neurotransmitter binds Cl-channel, Cl- flows into neuron.
3) Inside of the cell becomes slightly more negative
• more negative state termed inhibitory postsynaptic potential (IPSP)
4) Local current of ions becomes weaker.
• decreases in intensity with distance traveled toward initial segment
 Receptive Segment: Postsynaptic Potentials
Inhibitory postsynaptic potentials (IPSPs) are hyperpolarizations
caused by cation exit or anion entry

Figure 12.15b 23
 Receptive Segment: Postsynaptic Potentials

Figure 12.16 24
 Initial Segment
• Location
– Axon hillock
• Function
– Summation of EPSPs and IPSPs
– Voltage changes from the dendrites and soma are added
– May trigger an action potential (All or none law)
• You get an a.p. or you don’t, no inbetween
• Threshold membrane potential
– the minimum membrane potential needed to trigger an action
potential by opening voltage-gated channels
– about –55 mV
– multiple EPSPs must be added to reach threshold
25
 Initial Segment: Summation
Spatial Summation
• Multiple locations
on cell’s receptive
regions receive
neurotransmitter
simultaneously and
generate
postsynaptic
potentials

26
 Initial Segment: Summation
Temporal Summation
• A single
presynaptic neuron
repeatedly releases
neurotransmitter
and produces
multiple EPSPs
within a very short
period of time

27
 Conductive Segment
• Location
– axon
• Function
– Conduct Action potential
• Depolarization
– gain of positive charge as Na+ enters through voltage-
gated Na+ channels
• Repolarization
– return to negative potential as K+ exits through voltage-
gated K+ channels
– Propagation of a.p. is called an impulse or nerve signal

28
 Conductive Segment: Action Potential

• Action potentials = nerve signal

– Initiated at axon hillock
– Self-propagating along axon
– “All or None”
• If hit threshold will go
– All same strength (membrane changes from -70mV at rest to +30mV)
– Due to opening of voltage-gated channels
– Triggered at Threshold value
• minimum voltage change to open voltage-gated channel (-55mV)
• any value below this, a subthreshold value
 Conductive Segment: Action Potential
• Action potentials (continued)
– If threshold value reached
1. Depolarization
– Na+ channel opens, enters the neuron
» makes inside relatively positive (+30mV)
» flow of local current to adjacent areas
– opening of voltage-gated channels downstream
2. Repolarization
– sequential opening of voltage-gated K+ channels
» movement of K+ out of neuron returns membrane to RMP
» Returns to -70mV
3. Hyperpolarization
– K+ channels stay open and membrane becomes more negative then RMP
(~-85mV)
4. Return to RMP
– Na+/K+ pumps
 Generation of an Action Potential—Depolarization

Action potential: steps in

depolarization

1. At RMP, voltage-gated
channels are closed

2. As Na+ enters from adjacent

region, voltage-gated Na+
channels open

Figure 12.18a (part) 31

 Generation of an Action Potential--Depolarization

3. Na+ enters the axon causing

the membrane to have a
positive potential

4. Na+ channels close

becoming inactive (unable
to open) for a time

Steps 1–4 repeat in adjacent

regions and the impulse moves
toward synaptic knob

Figure 12.18a (part)

32
 Generation of an Action Potential—Repolarization

Action potential: steps in

repolarization

5. Depolarization slowly opens

K+ channels, and K+ diffuses
out, causing negative
membrane potential

6. K+ channels stay open for a

longer time, so K+ exit makes
cell more negative than RMP

Figure 12.18b (part)

33
 Generation of an Action Potential--Repolarization

7. K+ channels eventually close and RMP is reestablished

Steps 5–7 repeat in

adjacent regions as
the impulse moves
toward synaptic
knob

Figure 12.18b(part)
34
 Events of an Action Potential

Figure 12.19 35
 Conductive Segment: Continuous v.s.
Saltatory Conduction
• Continuous conduction
– unmyelinated axons
– Sequential opening of voltage-gated Na+ and K+ channels
• Saltatory conduction
– myelinated axons
– Action potentials propagated only at neurofibril nodes
– Myelinated regions
• with limited numbers of voltage gated Na+ and K+ channels
• well insulated, preventing ion movement
– Neurofibril nodes
• with large number of voltage-gated Na+ and K+ channels
• lack myelin insulation
• Where action potential occurs
Conductive Segment: Saltatory Conduction

K+ Na+ Diffusion of Na+

Neurofibril node Myelin sheath
through axoplasm

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

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

Action
potential
Repolarization Depolarization
 Transmissive Segment
• Location
– synaptic knob
• Function
– Release of neurotransmitter from neuron
• Events
1. Action potential reaches synaptic knob
2. Voltage-gated Ca2+ channels open
• movement of calcium ions into synaptic knob
3. Calcium triggers exocytosis of synaptic vesicles
4. Neurotransmitters released into synaptic cleft
• diffuse across cleft
• bind to specific receptors on cell to be stimulated
38
 Transmissive Segment:
Release of Neurotransmitter

Figure 12.22a 39
 Transmissive Segment

What is the sequence of events from the

arrival of an action potential at the synaptic
knob until the release of neurotransmitter
into the synaptic cleft?
 Events of Neuron Physiology

Figure 12.23, Panel 1 41

 Events of Neuron Physiology

Figure 12.23, Panel 2 42

 Events of Neuron Physiology

Figure 12.23, Panel 3 43

 Events of Neuron Physiology

Figure 12.23, Panel 4 44

 Velocity of Action Potential Propagation

• Factors influencing velocity of nerve signal

1. Diameter of axon
• larger diameter, faster the velocity of the signal
2. Myelination of axon
• more important factor
• faster velocity in myelinated axons