S8
Electrical and
concentration gradient
driving forces for
Sodium and Potassium
Size and
Direction
of Arrows
show
driving
forces!
What would
happen to
membrane
potential if
suddenly PNa
became very
great?
The G-H-K Equation!
Why is resting
membrane
potential closer
to EK than ENa?
How does the membrane potential
change if
1) permeability to sodium increases
2) Permeability to potassium increases
S9
The Goldman Hodgkin Katz
Equation
• If you know the concentrations of ALL
permeable ions and their relative
permeabilities, you can calculate the
membrane potential using the GHK
Equation.
S 10
At RMP, some Na+ leaks in, some K+ leaks out.
S 14
Which ion moving in
which direction (into or
out of cell) is responsible
for depolarization and
overshoot?
Which ion moving in
which direction (into or
out of cell) is responsible
for repolarization and
hyperpolarization?
Increase
PNa+
Can the membrane
potential go more
negative than -90 mV?
Increase
PK+
Increase
PK+
How do ions get across the membrane? Ion channels!
S 15
Leak Channels
Gated Channels
….. Ligand-gated
….. Mechanically-gated
….. Voltage-gated
Electrogenic SodiumPotassium ATP-ase maintains
concentrations across
membrane
Graded potentials are
conducted decrementally
for only a few millimeters,
die out over distance and
time, and are proportional
to the size of the stimulus.
3 Na+
2K+
S 17
Graded potentials are conducted no more than 2mm
Insect bites foot
(stimulus).
Sensory neuron
produces graded
potential in proportion
to intensity of the
stimulus.
How is signal
conducted to the brain?
S3
Types and locations of Ion Channels
Sensory neuron
Leak Channels
Gated Channels
….. Ligand-gated
….. Mechanically-gated
….. Voltage-gated
w/ LGCs and MGCs
Intracellular
Recording
Electrode or
Stimulating
Electrode
Interneurons & Motoneurons
w/ LGCs
w/ VGCs
S4
Expanded on next slide
What happens when the
membrane is
depolarized by more
than about 15 mV?
Action potentials are all or nothing.
Analogy of
shutter release
pressure on a
camera, either
trips shutter or
not.
How is the intensity of a
stimulus encoded by action
potential if all action potentials
have the same size (amplitude)?
S5
Relevance of the GHK equation
Changes in membrane
permeability produce changes in
membrane potential via the opening
and closing of ion channels!
S6
To reset from inactivated state
to closed state, membrane must
repolarize.
Open at -55 mV
Membrane must repolarize to
“reset” Na+ Channels to be
capable of opening again.
Compare and contrast voltagegated Na and K channels based on
time to open and duration of
open time.
S7
Voltage-gated Na+ channel
Tetrodotoxin from ovary of
Puffer fish, used in
Japanese sushi (fugu)
scienceblogs.com/.../upload/2006/03/channel.jpg
S8
What types of ion-channels are
labeled in this neuron in red?
TTX with red fluorescent marker
S9
Rising
Phase
Falling
Phase
Relative permeabilities
Duration of AP
Refractory periods
absolute RP
relative RP
Why does the
peak of the
action potential
not reach ENa?
Properties of V-gated
Na+ and K+ channels
account for the shape
of the action potential
and the refractory
periods.
S 10
S 11
Natural ways to Initate an
Action Potential
Graded depolarization in
cell body reach threshold
at axon hillock
Graded depolarization in
in receptive membranes of
sensory neurons reach
threshold for AP at trigger
zone. i.e. nociceptors and
stretch receptors.
Unstable membrane
potential cycles: pacemaker
potentials in pacemaker cells
of heart, smooth muscles of
gut, and medullary neurons
for respiratory rhythm.
S 12
Who
Cares?
Novacaine, lydocaine, xylocaine,
All block voltage-gated Na+ channels
Prevent action potentials, so stimulus
does not result in an action potential
in sensory neurons which would
convey that information to the brain
where person would be conscious of
the stimulus!
S 13
Questions About Action Potential Conduction:
How does an action potential move along the axon?
Why doesn’t the amplitude get smaller with distance?
Why is the conduction of an action potential unidirectional?
What is the absolute refractory period and what is going on with voltage gated sodium
channels that accounts for the absolute refractory period?
What is the relative refractory period and what is going on with voltage gated sodium
channels that accounts for the relative refractory period?
Axon
Hillock
Axon
S 14
In unmyelinated axons, action potential must be generated at each
point along the membrane, a relatively slow process that involves influx
of Na+ which sets up positive feedback cycle.
In myelinated axons, action potential must be generated only at the
nodes of Ranvier, which allows AP to be conducted much faster and
with fewer ions moving, and thus less energetically expensive.
S1
The Questions:
How does an action potential move along the axon?
Why doesn’t the amplitude get smaller with distance?
Why is the conduction of an action potential unidirectional?
Axon Hillock of
interneuron or
efferent neuron
Axon
Trigger Zone of
Sensory Neuron
S3
Saltatory Conduction
Figure 6.23
AP CV (up to 100 m/s)
Reminder: influx of Na+ is
very quickly followed by efflux
Location of channels
of K+ (not shown above)
Energy Requirements
Axon diameter
Clustering of V-gated channels at Nodes of Ranvier
What’s at the
end of an axon?
S4
Section C: Synapses and Synaptic Transmission
Figure 6.24
S5
Anatomy of an Electrical SynapseS 8
(aka Gap Junction)
Comparison to Chemical Synapses
• Directionality
• Response time
• Sign inversion?
Uncommon in human CNS.
Common in cardiac muscle
and some smooth muscle.
S6
Anatomy of a Chemical Synapse
Presynaptic cell
Postsynaptic cell
S7
Most neurotransmitters are synthesized
in the axon terminal.
Exceptions: Peptide NTs originate in cell
body, move in vesicles by fast orthograde
axonal transport to axon terminal.
Figure 6.27
Vesicle release proportional to
Ca++ influx (High f AP leads to
residual Ca++ in terminal)
Tetanus toxin & Botulinum
toxin disrupt SNARE function.
Fates of neurotransmitters:
1) Bind to receptor on Postsynaptic cell
2) Diffusion away from synapse
3) Enzymatic degradation
e.g. Acetylcholinesterase (AChE)
and Monoamine Oxidase (MAO)
4) Uptake by astrocytes
5) Reuptake into presynaptic
terminal (e.g. SSR)
S8
Presynaptic Facilitation
Presynaptic Inhibition
Mechanism: vary Ca++
entry in presynaptic
terminal B.
Size of PSP is
Variable!
Figure 6.33
Who Cares?
S1
Unidirectional
Release, diffusion, binding,
Post-synaptic Receptor Types: Inotropic or Metabotropic
Figure 6.25
Classification:
Excitatory (closer to
threshold for AP)
Or
Inhibitory (stabilizes
or hyperpolarizes)
S2
Types of Ligand-Gated Receptors
= ACH = Acetylcholine
Inotropic receptor
Metabotropic receptor
Agonist = Nicotine
Agonist = Muscarine
Antagonist = Curare
Antagonist = Atropine
Types of Acetylcholine Receptors so named for agonist:
Nicotinic AChR and Muscarinic AChR
S3
Priority by proximity
To axon hillock!
S4
Figure 6.28
EPSPs :which ion moving
in which direction?
Duration of PSP vs AP
Synaptic delay
Some ion Channels that allow flux of
Na+ and K+ simultaneously
e.g. nicotinic Acetylcholine Receptor
(nAChR)
S5
Figure 6.29
IPSPs :which ion moving
in which direction?
Some IPSPs result in no change in membrane
potential by opening Chloride channels that
stabilize membrane potential at resting value
(Nernst Potential for Cl- = -70mV) or in cells
that actively transport Cl- out.
EK+
S6
Figure 6.31
Summation and Synaptic Integration
Different times
Different locations
Challenge question: Suppose each IPSP hyperpolarizes by 5 mV and
each EPSP depolarizes by 5 mV.
If 4 inhibitory synapses are active at the same time, how many excitatory
synapses must be active simultaneously to exceed threshold (-55 mV) if
the resting membrane potential is -70mV?
S7
Synapses named for
NT used: -ergic
Examples:
Cholinergic
Adrenergic
Serotonergic
GABAergic
Peptidergic
S 11
Pharmacological agents intended to act in brain
must be able to cross blood-brain barrier.
Who Cares?
Parkinsons Disease
Treatments for Parkinsonism:
a) tablets of L-Dopa (which crosses the BBB) unlike Dopamine (which
would have widespread effects)
b) neuronal transplants (self, fetal, stem cell, pig),
c) electrical stimulation
NIH Stem Cell Information
S3
Touch, pain,
temperature,
proprioception
Vessel stretch,
O2, CO2, etc.
12 pairs of cranial nerves
31 pairs of spinal nerves
Vision, taste,
smell, hearing,
equilibrium
Skeletal
Muscle
Smooth muscle
Cardiac muscle
Glands
Tracts,
pathways,
commissures
Nuclei
Nerves & Ganglia
Control of digestive
functions in
quadraplegics via
enteric nervous system.
S4
Figure 6.38
S5
Components of gray matter
Figure 6.39
Amygdala &
Hippocampus
S6
How do we know the functions of various brain regions?
Analogy: experiments to
discover the function of a
battery in a car.
a) Correlations of deficits of
stroke victims with brain regions
affected.
b) Selective ablations.
c) Selective electrical and
chemical microstimulation
i) Dr. Hettes’s
experiments on rats
ii) Neurologist Wilder
Penfield & Epilepsy
S7
S8
Homunculus = representation of body parts
S9
Dorsal roots = sensory
(afferent)
Ventral roots = motor
(efferent, both somatic and
autonomic)
Gray matter regions of brain
and spinal cord
“Pinched nerves” and bulging
discs
Ascending and descending
axonal tracts in white matter
not anatomically delineated.
Atlanta-Boston flight
Origin-Destination
Naming of white
matter tracts…..
S 10
Explanation for Cervical and lumbar
enlargements of spinal cord.
Spinal nerves named for vertebral level.
8
12
5
5
1
Using patient’s localization of symptoms with
knowledge of dermatomes to determine
which spinal nerve is affected by damage.
Epidural injections into region of cauda
equina of Lidocaine-like agents to block
action potentials in sensory and motor axons
without risk of damage to spinal cord.
S1
Homunculus = representation of body parts
Somatotopy = adjacent regions of the body are represented
by adjacent regions in the cerebral cortex.
S3
Dermatomes
Who
cares?
Surgery for
chronic back
pain
How might this information
be clinically useful?
S4
Cranial Nerves
Challenge: Identify
the deficits associated
with damage to a
given cranial nerve.
S5
On
Old
Olympus’
Vision
Treeless
Top
A
Fat
Hearing & Equilibrium
!!!
Spinal
S6
Figure 6.43
ACh & mAChR
Locations of neuronal cell bodies, ganglia, pharmacology of the
neuromuscular junction (NMJ) at skeletal muscle (nAChR)
Diagram of NMJ compared to synaptic varicosities characteristic of
autonomic postganglionic axons.
Locations and proximities of target cells and distributions of receptors on
target cells.
Somatic = excitatory only at NMJ (ex. Reduced muscle tone)
Autonomic= exitatory or inhibitory depending on NTs and their receptors.
Sympathetic (thoraco-lumbar) division
Parasympathetic (cranio-sacral) division)
S7
Figure 6.44
S8
Why activation of the
sympathetic division has
widespread effects.
S8
Antagonist = Curare
Figure 6.46
Antagonist = Atropine
Adrenal medulla is modified sympathetic ganglion that
secretes mainly EPI
S9
S 10
mAChR
Table 6.11
Emotional
Thermoregulatory