Neurons





A nerve cell capable of generating and transmitting electrical signals
Vary in structure and properties
Use the same basic mechanisms to send signals
Generate action potentials or passive potential
Communicate with other neurons or cells via synaptic connections
(electrical or chemical)
Neurons
Structural Diversity of Neurons
Figure 5.18a
Neuron Classification Based on Structure
Figure 5.18c
Neuron Classification Based on Function
Figure 5.18b
Neural Zones
Four functional zones
 Signal reception: dendrites and the cell body (soma)
- Incoming signal is received and converted to a change in
membrane potential
 Signal integration: axon hillock
- Strong signal  action potential (AP)
 Signal conduction: axon; some wrapped in myelin sheath
- AP travels down axon
 Signal transmission: axon terminals
- Neurotransmitter is released
Neural Zones, Cont.
Figure 5.2
Electrical Signals in Neurons
Neurons have a resting membrane
potential (like all cells)
Neurons are excitable; can rapidly change
their membrane potential
Changes in membrane potential act as
electrical signals
Figure 5.3
Measuring the voltage
Use microelectrodes to measure the voltage between
outside and inside
Conducting fluid such as KCL is used
Reference electrode is placed in the bathing medium
Potentiometer will measure
the potential ie
resting potential
Membrane Potential
Three factors contribute to the membrane
potential
The distribution of ions across the plasma
membrane
The relative permeability of the membrane
to these ions
The charges of the ions
►Nernst equation can be used to measure
the potential of a cell ie the voltage
difference between the inside and the
outside of the cell.
Membrane Potential
EK+ = (1.9872*295)/(1*23062) ln (4/139) = - 88 mV at 22oC
ENa+ = (1.9872*295)/(1*23062) ln (145/12) = 62 mV at 22oC
ECl- = (1.9872*295)/(-1*23062) ln (116/4) = - 84 mV at 22oC
Resting potential
Origin of the resting potential in a typical vertebrate neuron.
 A- - negatively charged proteins
 Resting neuron: 10 times more open
K+ channels than Na+ or Cl- channels
 Outside of cell is more positive relative
to the inside of the cell
 K+ is dominant because its
permeability is greatest (PK). This is
due to leak channels
 So the resting potential is closest to
the Nernst potential for K+
 Also have leakage of Na+ (PNa) and Cl(PCl)
Resting potential
Actual measurements of membrane potential
 Measured in giant axon of squid
 Found resting potential of -65 to -70
mV
 Increased external K+ to determine
new membrane potential
 Found a slope of – 58 mV ► means
that for every ten fold increase in
external K+ the potential will increase
by 58 mV at room temperature
 So other ions are influencing the
resting potential!!
 Permeability of Na+ and Cl- ions and
the presence of proteins.
 Use Goldman equation to calculate the
resting potential
Resting potential
Membrane Potential
Nernst equation predicts membrane potential for a single
ion
Goldman equation for the membrane potential (Em):
predicts the membrane potential using multiple ions
RT PK [ K  ]o  P NA [ Na  ]o  PCl [Cl  ]i
Em 
ln
F
PK [ K  ]i  PNA [ Na  ]i  PCl [Cl  ]o
Chloride ion has a charge opposite to the two cations, a correction is needed
to prevent the cations and anion from canceling each other.
Thus, the statement of relative chloride ion concentrations is inverted—
inside over outside
In the giant squid:
PK+ : PNa+ : PCl- = 1 : 0.04 : 0.45
Membrane Potential
Effects of changing the ion permeability
The resting membrane potential is -53 mV; ENa, EK, and ECl are the potentials
calculated from the Nernst equation if the membrane contains only open channels for
Na+ or K+ or Cl-, respectively.
Membrane Potential
Lets do some calculations 
Electrical signals
Changes in Channel permeability create Electrical
signals!
• Mechanically gated ion channels
• Sensory neurons. Open in response to pressure or stretch
• Chemically gated ion channels
• Respond to ligands
• Voltage gated Na+ channels
• Respond o changes in membrane potential
• Voltage gated K+ channels or CA2+ channels
Graded Potential vs. Action Potential
Two types of electrical signals
Action potentials
Active conduction
 Passive conduction of signal is limited by properties of
the nerve and signal is reduced over distance
 Active conduction ie action potentials (AP)
- Signal travels along nerve with no loss of amplitude
Action Potentials (AP)
• Occurs only when the
membrane potential at
the axon hillock reaches
threshold
• Three phases
• Depolarization
• Repolarization
• Hyperpolarization
• Absolute refractory
period – incapable of
generating a new AP
• Relative refractory period
– more difficult to
generate a new AP
Figure 5.10
Voltage-Gated Channels
• Change shape due to changes in membrane
potential
• Positive feedback, e.g., influx of Na+   local
depolarization   number of open Na+
channels
• Na+ channels open first (depolarization)
• K+ channels open more sloooooowly
(repolarization)
• Na+ channels close
• K+ channels close slooooowly (relative refractory
period)
Channels of an Action potentials
Voltage gated Na+ channels:
3 states: closed, open, inactive
Closed to open:
- Depolarization is necessary to open the channel
- Acts to activate itself in a regenerative cycle
- More Na+ influx depolarizes the membrane which opens more channels
which depolarizes the membrane more.
Open to Inactive:
- Depolarization is also necessary to inactive the channel
- Once the channel is open it will then also switch to the inactive state
and can not be opened again
Inactive to closed:
- The channel will not switch back to the closed state until the membrane
has repolarized (i.e. gone back towards the original resting membrane
potential
- Once in the closed state it can then be reopened
Na+ Channels Have Two Gates
• Activation gate – voltage dependent
• Inactivation gate – time-dependent
Na+ Channels Have Two Gates
Channels of an Action potentials
Voltage gated K+ channels (delayed rectifying K+ channel):
2 states: closed and open
Closed to open:
- Strong depolarization is necessary to open the channel
- Hyperpolarizes the cell
-
Brings membrane back towards Nernst potential for K+
Open to Closed:
- Will close when the membrane becomes hyperpolarized
- Works to shut itself down
Voltage-Gated Channels, step by step
Figure 5.12
Action Potentials Travel Loooong Distances
• “All-or-none” – occurs or does not occur;
identical without degradation
• Self propagating - an AP triggers the next
AP in adjacent areas of the axonal
membrane
• Electronic current spread in between ion
channels
• Cycle: Ion entry  electronic current
spread  triggering AP
Components of an Action potentials
Components of an Action potentials
Threshold
 Most neurons have a threshold at -50 mV (i.e. 10 to 15 mV depolarization)
 Action potential is an all or none event. If a nerve is at rest the amplitude
on one action potential will be the same all along the nerve independent of the
stimulus strength
 Threshold reflects the need to trigger the opening of the
voltage-gated sodium channel (need a depolarization of about
10 to 15 mV to open)
Rising phase




Sodium channels open
Na+ ions flow into cell
Depolarizes the cell
More and more sodium channels open
= a regenerative response
regenerative opening of sodium
channels drives the membrane potential
towards a peak of the Nernst equilibrium
potential for Na+
Components of an Action potentials
Peak
 During an action potential the membrane potential goes towards the
Nernst equilibrium potential for Na+
 In terms of Goldman-Katz equation now permeability to Na+ is dominant
(K+ and Cl- minor components) therefore membrane potential goes towards
ENa
 Usually falls short of ENa, less driving force on Na+ and the channels begin
to inactivate rapidly after activation
Components of an Action potentials
Fall
 Membrane potential falls back towards rest
- Why doesn't the action potential stay around ENa?
Two reasons:
i) Na+ channels move into an inactive state
ii) delayed K+ channels open
 Inactivating Na+ channels
- Na+ channels go to an inactivated state after 1-2 msec after first opening
- inactivated = can NOT be reopened
- Membrane potential now determined mostly by K+
(same as for resting potential) and membrane starts to repolarize
 Delayed K+ channels open (delayed rectifier; voltage-gated like Na+ channel)
- open after about 1-2 msec of threshold depolarization
- now K+ flows out of the cell and speeds the repolarization process
- cause the hyperpolarization after the action potential
- open K+ channels make the K+ permeability higher than at rest
- membrane more negative on inside
- hyperpolarization of membrane causes K+ channels to close
- Membrane settles back to rest
Components of an Action potentials
Repolarization
 Voltage-gated Na+ channels and voltage-gated K+ channels now closed
 Membrane goes back to the resting state
- i.e. the leak channels are the only channels open and again
set the membrane potential
Refractory period (RP)
Absolute RP
 Na+ channels are inactive and CAN NOT be opened no matter how much
the membrane is depolarized at this time
 another action potential can not be generated
Relative RP
 as membrane repolarizes ---goes to more negative potentials
 this triggers the Na+ channels to move
from an inactive state to a close state
 hyperpolarization by the opening of the
K+ channels helps this process
 once Na+ channel is in the closed state
it can be opened again with depolarization
 during relative RP, more and more
Na+ channels available to be opened and
therefore increase the chances of firing
an action potential
Refractory period (RP)
Frequency of AP
How does a nerve communicate the strength of a stimulus?
 Information is given by the frequency of the AP along the nerve
 Stimulus strength triggers different frequency of AP
 For example: light touch – infrequent AP;
rough touch – more frequent AP
 Refractory period limits the frequency of AP
 During the relative RP an AP can be generated
but has to be at supra threshold because it has to
overcome the hyperpolarization
 Will be at decreased amplitude because
fewer Na+ channels are available to open
Direction of AP
Unidirectional conduction of an action potential due to transient
inactivation of voltage-gated Na+ channels
Action Potentials Travel Loooong Distances
• Triggered by the net
graded potential at the
axon hillock
(trigger zone)
• Do not degrade
• Travel looong distances
• All-or-none
• Must reach threshold
potential to fire
Figure 5.7
Action Potentials Travel Looong Distances
Figure 5.13 (1 of 2)
Action Potentials Travel Looong Distances
Figure 5.13 (2 of 2)
Signals in the Dendrites and Cell Body
•
•
Incoming signal, e.g., neurotransmitter
Membrane-bound receptors transduce the chemical signal
to an electrical signal by changing the membrane potential
(graded potential)
Graded Potentials
• Vary in magnitude depending on the strength of the stimulus
• e.g., more neurotransmitter  more ion channels will open
Graded Potentials
• Ions move down an
electrochemical gradient
• Net movement stops when
the equilibrium potential is
reached
• Can depolarize (Na+ and
Ca2+ channels) or
hyperpolarize (K+ and Clchannels) the cell
Graded Potentials Travel Short Distances
• Conduction with decrement –  strength with 
distance from opened ion channel
• Due to
• Leakage of charged ions across the membrane
• Electrical resistance of the cytoplasm
• Electrical properties of the membrane
• Electrotonic current spread – positive charge
spreads through the cytoplasm causing
depolarization of the membrane
• Can be excitatory or inhibitory
Graded Potentials Travel Short Distances
Integration of Graded Signals
• Many graded potentials can
be generated simultaneously
• Many receptor sites
• Many kinds of receptors
• Temporal summation –
graded potentials that occur
at slightly different times can
influence the net change
• Spatial summation – graded
potentials from different sites
can influence the net change
Figure 5.9
Spatial summation
Temporal summation
Integration of Graded Signals, Cont.
Figure 5.8
Back to Neuron structure
Myelination
• Vertebrate neurons are myelinated
• Myelin – insulating layer of lipid-rich Schwann cells wrapped
around the axon
• Glial cells – supportive neural cells, e.g., Schwann cells
Myelination, Cont.
Figure 5.14
Myelination, Cont.
• Nodes of Ranvier – areas of exposed axonal membrane in
between Schwann cells
• Internodes – the myelinated region
• Saltatory conduction – APs “leap” from node to node; APs
at nodes of Ranvier and electrotonic current spread
through internodes
Myelinated Neurons in Vertebrates
Disadvantage of large axons
• Take up a lot of space which limits the number
of neurons that can be packed into the
nervous system
• Have large volumes of cytoplasm making
them expensive to produce and maintain
Myelin enables rapid signal conduction in a
compact space
Myelin Increases Conduction Speed
•  membrane resistance: act as insulators
  current loss through leak channels 
 membrane resistance   l
•  capacitance:  thickness of insulating
layer   capacitance   time to
constant of membrane   conduction
speed
• Nodes of Ranvier are needed to boost
depolarization
Glial Cells
• Most neural cells (90% in human brain)
• Cannot generate APs
• Five main types
• Schwann cell – form myelin in motor
and sensory neurons of the PNS
• Oligodendrocyte – form myelin in the
CNS
• Astrocyte – transport nutrients, remove
debris in CNS
• Microglia – Remove debris and dead
cells from CNS
• Ependymal cells – line the fluid-filled
cavities of the CNS
Figure 5.19
Unidirectional Signals
• Stimulus starts at the axon hillock and
travels towards the axon terminal
• Up-stream Na+ channels (just recently
produced an AP) are in the absolute
refractory period
• The absolute refractory period prevents
backward transmission and summation of
APs
• Relatively refractory period also
contributes by requiring a very strong
stimulus to cause an AP
The Synapse
• Signal transmission zone
• Synapse – synaptic cleft, presynaptic cell, and
postsynaptic cell
• Synaptic cleft – space in between the
presynaptic and postsynaptic cell
• Postsynaptic cell – neurons, muscles, and
endocrine glands
• Neuromuscular junction – synapse between a
motor neuron and a muscle
Diversity of Synaptic Transmission
Figure 5.26
Electrical and Chemical Synapses
Electrical synapse
Chemical synapse
Rare in complex animals Common in complex
animals
Common in simple
Rare in simple animals
animals
Fast
Slow
Bi-directional
Unidirectional
Postsynaptic signal is
similar to presynaptic
Excitatory
Postsynaptic signal can
be different
Excitatory or inhibitory
Chemical Synapse Diversity
Vary in structure and location
Figure 5.27
Neurotransmitters
Characteristics
• Synthesized in neurons
• Released at the presynaptic cell following
depolarization
• Bind to a postsynaptic receptor and causes
an effect
Neurotransmitters, Cont.
More than 50 known substances
Categories
•
•
•
•
•
Amino acids
Neuropeptides
Biogenic amines
Acetylcholine
Miscellaneous
Neurons can synthesize many kinds of
neurotransmitters
Neurotransmitter Action
Inhibitory neurotransmitters
• Cause hyperpolarization
• Make postsynaptic cell less likely to generate
an AP
Excitatory neurotransmitters
• Cause depolarization
• Make postsynaptic cell more likely to generate
an AP
Neurotransmitter Receptor Function
Ionotropic
• Ligand-gated ion channels
• Fast
• e.g., nicotinic ACh
Metabotropic
• Channel changes shape
• Signal transmitted via
secondary messenger
• Ultimately sends signal to
an ion channel
• Slow
• Long-term changes
Figure 5.28
Ca2+ Regulates Neurotransmitter Release
Figure 5.16
Amount of Neurotransmitter
•
•
•
Influenced by AP frequency which influences Ca2+
concentration
Control of [Ca2+]
• Open voltage-gated Ca2+ channels  [Ca2+]
• Binding with intracellular buffers  [Ca2+]
• Ca2+ ATPases  [Ca2+]
High AP frequency  influx is greater than removal 
high [Ca2+]  many synaptic vesicles release their
contents  high [neurotransmitter]
Acetylcholine
Primary neurotransmitter at the vertebrate
neuromuscular junction
Figure 5.17
Synaptic Plasticity
• Change in synaptic function in response to patterns of
use
• Synaptic facilitation –  APs   neurotransmitter
release
• Synaptic depression –  APs   neurotransmitter
release
• Post-tetanic potentiation (PTP) – after a train of high
frequency APs   neurotransmitter release
Figure 5.32
Long-term potentiation
Postsynaptic Cells
Have specific receptors for specific
neurotransmitters
e.g., Nicotinic ACh receptors
Signal Strength
• Influenced by neurotransmitter amount and receptor
activity
• Neurotransmitter amount: Rate of release vs. rate of
removal
• Release: due to frequency of APs
• Removal
• Passive diffusion out of synapse
• Degradation by synaptic enzymes
• Uptake by surrounding cells
• Receptor activity: density of receptors on postsynaptic
cell
Diversity of Signal Conduction
So far:
•
•
•
•
Electrotonic
Action potentials
Saltatory conduction
Chemical and electrical synapses
Also:
• Shape and speed of action potential
• Due to diversity of Na+ and K+ channels
Ion Channel Isoforms
•
•
•
•
•
Multiple isoforms
Encoded by many genes
Variants of the same protein
Voltage-gated K+ channels are highly diverse (18 genes
encode for 50 isoforms in mammals)
Na+ channels are less diverse (11 isoforms in mammals)
Table 5.2
Channel Density
Higher density of voltage-gated Na+
channels
 Lower threshold
 Shorter relative refractory period
Voltage-Gated Ca2+ Channels
• Open at the same time or instead of
voltage-gated Na+ channels
• Ca2+ enters the cell causing a
depolarization
• Ca2+ influx is slower and more sustained
• Slower rate of APs due to a longer
refractory period
• Critical to the functioning of cardiac muscle
Conduction Speed
Two ways to increase speed: myelin and
increasing the diameter of the axon
Table 5.3
Cable Properties
• Similar physical principals govern current flow
through axons and telephone cables
• Current (I) – amount of charge moving past a
point at a given time
• A function of the drop in voltage (V) across the circuit
and the resistance (R) of the circuit
• Voltage – energy carried by a unit charge
• Resistance – force opposing the flow of
electrical current
• Ohm’s law: V = IR
Cable Properties, Cont.
• Ions moving through voltage-gated channels cause a
current across the membrane
• Current spreads electrotonically
• Some current leaks out of the axon, and flows
backwards along the outside of the axon, completing the
circuit
Figure 5.20ab
Cable Properties, Cont.
Each area of axon consists of an electrical
circuit
• Three resisters: extracellular fluid (Re), the
membrane (Rm), and the cytoplasm (Rc)
• A capacitor (Cm) – stores electrical charge; two
conducting materials (ICF and ECF) and an
insulating layer (phospholipids)
Figure 5.20c
Voltage Decreases With Distance
•
•
•
•
•
Conduction with decrement
Due to resistance
Intracellular fluid: high resistance   decrement
Extracellular fluid: high resistance   decrement
Membrane: high resistance   decrement
• K+ leak channels (always open): some + charge leaks
out   current
• Few K+ leak channels   + charge leak out  high
membrane resistance
Length Constant (l)
•
•
•
Distance over which
change in membrane
potential will decrease
by 37% (1/e)
ro is usually low and
constant
l is largest when rm is
high and ri is low
l  rm /(ri  r )
o
l  rm / ri
Figure 5.21
Speed of Conduction and Resistance
• Axonal conduction is a combination of
electrotonic current flow and APs
• Electrotonic current flow is much faster
than APs
• But, electronic current flow is graded and
can travel only short distances
• Greater l  more electrotonic current flow
/APs  faster speed of conduction
Speed of Conduction and Capacitance
• Capacitance – quantity of charge needed to
create a potential difference between two
surfaces of a capacitor
• Depends on three features of the capacitor
• Material properties: generally the same in cells
• Area of the two conducting surfaces:  area  
capacitance
• Thickness of the insulating layer:  thickness  
capacitance
Speed of Conduction and Capacitance
• Time constant (t) - time needed to charge the
capacitor; t = rmcm
• Low rm or cm  low t  capacitor becomes full
faster  faster depolarization  faster
conduction
Giant Axons
• Easily visible to the naked eye
• Not present in mammals
Figure 5.24
Giant Axons Have High Conduction Speed
• rm is inversely proportion to surface area: 
diameter   surface area   leak channels
  resistance
• ri is inversely proportional to volume:  diameter
  volume   resistance
l  rm / ri
• Effect of resistance
•  rm   l   conduction speed
•  ri   l   conduction speed
• Do not cancel each other out: rm is proportional
to radius, ri is proportional to radius2
• Therefore, net effect of increasing radius of the
axon is to increase the speed of conduction
Giant Axons Have High Conduction Speed
Figure 5.25