Download Action Potential

Non-neuronal cells in the CNS (glia):
10-100x more abundant
Macroglia: large non-neuronal cells
1. astrocytes (star shaped) –
mostly located near axons and dendrites
WHY ???
Functions: a. insulate axons/dendrites (non-myelin sheath)
b. Provide many nutrients for neurons
c. “Astrogliosis”: engulf damaged neurons,
degrade them. “glial scar” at injury site
d. Help neurons become “excited” by
releasing potassium (K+) under certain
conditions
2. Oligodendrocytes: “oligo”… (few dendrites)
- found everywhere near neurons
Main functions: INSULATION !!
form myelin sheath
called “Schwann cells” in peripheral NS
called oligodendrocytes in CNS
3. Radial Glia:
Radial glial cells act as guide wires for the migration of neurons
- long processes,
very important for
development of brain
in embryos/fetuses
-
Targets of many substances (ex. alcohol)
that are “teratogens”
Nature Reviews:
Neuroscience, 2, 287-293
4. Ependymal Cells:
- line walls of cerebral ventricles, make/secrete CSF
- projections (flagella) extend into ventricles and “flutter”
to produce motion of CSF so it will leave ventricle
Rabbit lateral ventricl
Adapted from Haines, D.E.
Neuroanatomy: An atlas of structures,
sections, and systems, 5th ed. Lippincott
Williams & Wilkins, Baltimore, 2000
Neural activity: how a neuron works
(1)
physical properties of neuronal membrane
cell body - axon - dendrites
(2)
presence of ion channels (or receptors) in membrane
(3)
electrical potential across the membrane
WHY DO WE NEED TO KNOW THIS ?!!!!!!!!!!!!!
(1)
neurophysiology correlates with behavior
for many clinical disorders
(2)
neurophysiology can produce treatments
Definitions:
“Ion”: a molecule that unequal # of electrons and protons?
- molecule has positive (+) or negative (-) charge
“Electrical Potential”: difference in concentration of “+” and
“-” charged moleculars inside vs outside neuron
Important Ions:
Sodium (Na+), Calcium (Ca2+), Potassium (K+),
chloride (Cl-)
How neurons communicate:

Neurons communicate by means of an
electrical signal called the “Action Potential”

Action Potentials are based on movements of
ions between the outside and inside of the
cell

When an Action Potential occurs a chemical
message is sent to neighboring neurons
Action potential is an electrical event inside of a single neuron
-involves movement of ions in or out of neuron
“Neurotransmission” is chemical communication between 2 or more
- involves a neuron release a “neurotransmitter” to contact
a nearby neuron(s)
The Neuron Membrane
Physical Properties of Membrane
Outside
Inside
* lipid bilayer- provides control of what gets in
1. not permeable to water or most
anything else.
-exceptions ?
2.
non-rigid
ion channels
Neurotransmitter receptors
Properties of Ion Channels and Receptors:
1)
proteins
extend from extracellular to intracelluar
2)
highly specific for particular ions
3)
opening and closing are tightly regulated
open only in specific situations
Electrical Potential Across Membrane:
* difference in + vs - charge from
outside to inside of cell
recording electrode
reference electrode
axon
extracellular fluid
Outside of Neuron
K+
Na+
Ca2+
Cl-
Cell Membrane “at rest”
K+
Na+
Cl-
-
Ca2+
Inside of Neuron
Potassium: more inside than outside
Sodium: more outside than inside
Chloride: more outside than inside
Calcium: more outside than inside
Negatively (-) charged
Proteins
- Lots of these !!!
***** Negative Resting Potential *****
Expressed in “milliVolts (mV)”
what is the potential ?
why is it negative ?
- 70 mV
Large negatively charged
proteins
resting potential is close to
potential needed to “fire” = neurotransmitter release
How does it stay near the resting potential ?
1. Potassium equilibrium potential
2. Na-K+ exchanger
3. Inward rectifying K+ channels and Ca2+ channels ?
Most ions only get into a neuron if a membrane receptor or ion
channel open, don’t flow across neuron membrane freely…
1 ion does flow in and out of neuron along its
“concentration gradient” : ion easily crosses membrane according
Neurons don’t want most ions to flow across the concentration
gradient because that would cause constant electrical activity and
eventual neuron death…
1. K+ equilibrium potential: only K+ flows across membrane
according to the concentration
gradient
*** Other ions only get in when receptors
or channels are forced open
At rest, more K+ outside of cell – so K+ wants to flow out to
equalize
intra- and extracellular concentrations.
But, as K+ flows out of cell, inside becomes more negative
(because of large intracellular proteins). This negative
charge attracts K+
remember, opposites attract !!
So, the resting membrane potential represents the balance
between
1. K+ wanting to flow out of cell because of concentration
gradient
2. negative proteins attracting K+ to stay in cell
2. Na-K+ exchanger: some sodium (Na) does leak into the
cell, at all times.
So, neurons have a “pump” that pushes Na+ back out of
the cell when concentrations get too high (which can
happen in a matter of minutes)
So, why doesn’t this Na outflow make inside
even more
negative ??
K+ comes in through the same pump
that ejects Na
http://pharma2010.wordpress.com/2008/09/08/chemicalsynapes/
3. Inward “rectification” of K+ levels:
“K+ channels that primarily allow K+ in cells only under
specific conditions…”
-serve a very specific function, maintaining the
membrane at rest.
What Happens when the potential is changed ?
A neuron either is more or less likely to fire
(1)
Depolarizing stimulus - reduced potential
at -50 mV, Action Potential
what drives the action potential ?
Na+ channels open for milliseconds
at +40 mV, these close
K+ outflow repolarizes the potential
* small undershoot
where does this occur ??
cell body
axon
Axon hillock
dendrites
How does the action potential have an effect ?
propagation- action potential progresses down
the cell membrane by segments.
one region is stimulated, then the region next to it is, etc.
electrical current changes shape of
channels in adjacent regions
* Na+ channels
Axonal properties of propagation:
(1) voltage-sensitive Na+ channels
(2) where are these Na+ channels ?
Axon (magnified)
myelin
nodes of Ranvier
saltatory conduction- “jumping”

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At rest the inside of the cell is at -70 mV
With inputs to dendrites inside becomes more positive
if resting potential rises above threshold an action
potential starts to travel from cell body down the axon
Figure shows resting axon being approached by an AP
Dr. Wayne Shebilske
Wright State University
Depolarization ahead of AP



AP opens cell membrane to allow sodium (NA+) in
inside of cell rapidly becomes more positive than outside
this depolarization travels down the axon as leading edge
of the AP
Dr. Wayne Shebilske
Wright State University
Repolarization follows


After depolarization potassium (K+) moves out
restoring the inside to a negative voltage
This is called repolarization
Dr. Wayne Shebilske
Wright State University
Finally, Hyperpolarization

Repolarization leads to a voltage below the resting
potential, called hyperpolarization

Now neuron cannot produce a new action potential

This is the refractory period

What else might cause a “hyperpolarization” ?
Dr. Wayne Shebilske
Wright State University
What happens when the current gets to the end of axon ?
electrical
vs.
chemical communication between neurons
Otto Loewi- using isolated frog heart in physiological fluid
electric stimulation slowed it down
applied fluid to another frog heart
slowed it down
A.
B.
Ca2+
C.
Ca2+
A. nerve impulse arrives at terminal
deforms voltage gates Ca2+ channels
B. Ca2+ flows in
microtubules attached to vesicles contract
vesicle fuse with terminal membrane
C. vesicles burst, release neurotransmitter in synaptic cleft
How does neurotransmitter release change membrane
potential of another cell ?
cell body
axon
dendrites
Presynaptic terminal ends at a body, axon or dendrite
a receptor protein for NT must be present
1. excitatory post-synaptic potential (EPSP)
NT-receptor interaction causes small depolarization
Spatial Summation
0
-50
-70
Temporal Summation
2. inhibitory post-synaptic potential (IPSP)
NT-receptor interaction causes hyperpolarization
0
-50
-70
Why an EPSP or an IPSP ?
1. neurotransmitter.
acetylcholine, dopamine, serotonin,
norepinephrine, glutamate, GABA
2. specific type of receptor
one neurotransmitter can produce
an EPSP or an IPSP, depending on receptor
EPSP
Na+ , Ca2+ or K+
IPSP
Cl-
Receptor can be an ion channel
binding site
Ionotropic Receptors are comprised of:
1. multiple subunits
different proteins link together
2. a core which is permeable to
one or a few ions
3. binding site on extracellular portion
characteristics:
fast acting
brief in duration
Either excitatory or inhibitory
Inhibitory Ionotropic Receptors: IPSP, Cl-
Drugs of abuse ???
ethanol - barbiturates - benzodiazepines
Excitatory Ionotropic Receptors : Na+, K+ ,Ca2+
- nicotine ?
II. Metabotropic Receptors
G proteins
(guanine nucleotide binding)
Metabotropic Receptors are comprised of:
1. a single polypeptide
2. binds to G proteins
3. binding site
1. G proteins “α” subunit “breaks off when NT binds”
2. activate second messengers , binds to other receptors
binds to ion channels
Either excitatory or inhibitory
Characteristics:
slow acting
longer in duration
What happens to Neurotransmitter after
Acting at Postsynaptic Site ?
1. enzymatic
breakdown
2. re-uptake by
transporter
used to make
more NT
reabsorbed by
vesicles
efficient - takes more energy to start over
essential amino acids
enzymatic processes
Serotonin (5-hydroxytryptamine or 5-HT)
reuptake is a major focus of drug development effort
WHY ??
Some peculiarities of actions potentials
Not all neurons “fire” at same potential ( -50 mV)
1. neurons with larger axons require less
depolarization
-specialized to carry information
more rapidly ??
2. some granule cells release small amounts of
transmitter without having action potentials (do
have small depolarization)
3. in some neurons, Na doesn’t drive the “spike” of
the action potential- it’s Ca2+
5. Most action potentials last for less than ½ of a
msec , but some action potentials are slow to
develop and last minutes
6. “Gap Junctions”- exceptions to the “chemical synapse”
1. Close physical contact
2. Electrical current decays
in cell 2
3. Current bi-directional
(usually)
4. Speed of transmission ?
Speed of response “
5. Where do you see these ?
Neurotransmitters

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Acetylcholine
Serotonin
Norepinephrine
Dopamine
Endorphins
GABA
Glutamate
-Synthesized in neurons, stored in synaptic vesicles
-Release by an Action Potential
-Activate receptors on another neuron
-on dendrites, soma, or axons
Acetylcholine (ACh)

Found in “neuromuscular junction”
- here motor nerves touch muscle

Involved in muscle movements and
function of involuntary muscles
- breathing, heart muscle activity
Why are acetylcholine receptors important ??

Curare - blocks ACh receptors


paralysis results
Nerve gases and Black Widow spider
venom - too much ACh leads to
severe muscle spasms and possible
death

Cigarettes - nicotine works on
ACh receptors

can artificially stimulate skeletal
muscles, leading to slight, trembling
movements

Can also increase heart rate,
breathing rate
Alzheimer’s Disease


Deterioration of
memory, reasoning and
language skills
Symptoms may be due
to loss of ACh neurons
Where is it ?
midbrain
Basal forebrain
pons
medulla
Basal forebrain– sends axons to cortex, hippocampus
Cognition, judgement,
Reflexes, sensory processes
Serotonin (5-HT)

Involved in sleep
cause drowsiness

Involved in depression
SSRI’s (selective serotonin reuptake inhibitors) works
by keeping serotonin in the synapse
longer, giving it more time to exert an
effect
Involved in sexual behavior
increasing serotonin in one
brainstem nucleus = loss of sexual
sensation

Where is it ?
Raphe nuclei
Raphe nuclei: project to thalamus
basal ganglia
hippocampus
cortex
Cognition, motor function, mood, sensory processing
Norepinephrine (NE)
(aka. “adrenaline” )

“Fight or flight” response
released from adrenal gland
AND made by neurons
both a neurotransmitter and
a hormone
- any substance released by a gland into the bloodstream
Arousal = a brain stem nucleus
in “reticular formation” influences
your cogntive arousal

Where is it ?
Locus coeruleus
Locus coeruleus – projects to basal ganglia
hippocampus
cortex
Cognition, memory, motor function…
Dopamine (DA)

Involved in movement, attention and
learning
Loss of dopamine- producing
neurons is cause of Parkinson’s
Disease

Dopamine imbalance also involved in
schizophrenia

Required to experience “pleasure”
- “meso-limbic” DA system
Midbrain
limbic system
Neurons in midbrain, send axons to forebrain (limbic system), release DA
Where is it ?
Meso-limbo-cortical
Mes-striatal
Meso-limbo-cortical: projects to nucleus accumbes
cortex
hippocampus
Drug reward, cognition, memory, sensory processes…
Meso-striatal: projects to striatum
Movement
Endorphins
- part of brains normal response to pain

Control pain and pleasure

Released in response to pain

Morphine and codeine work on
endorphin receptors Involved in
healing effects of acupuncture

Everywhere in the brain !!!
Gamma-Aminobutyric Acid
(GABA)

Main inhibitory neurotransmitter

Benzodiazepines (which include
tranquilizers such as Valium) and
alcohol work on GABA receptor
complexes

Everywhere in the brain !!
Glutamate

Major excitatory neurotransmitter

Too much glutamate (and too little
GABA) associated with epileptic
seizures

Everywhere in the brain !!!

Very important for learning/memory
Hormones

Chemical messengers secreted into
bloodstream
Hormonal communication
Endocrine
cells
Bloodstream
Target
cells
Hormones vs.
Neurotransmitters

Distance traveled between release and
target sites
 hormones travel longer distances (feet)
 neurotransmitters - travel across a
synaptic cleft (20 nm)

Speed of communication
 hormones - slower communication
 neurotransmitters - rapid, specific
action
Hormones

Released by organs, including the
stomach, intestines, kidneys and
the even neurons

Also released by a set of glands
called the endocrine system

Includes:

hypothalamus

pituitary gland
adrenal glands
thyroid gland
parathyroid glands
pineal gland
pancreas
ovaries and testes

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Hypothalamus and
Hormones

Hypothalamus releases releasing factors
which in turn cause pituitary gland to
release trophic hormones

“releasing hormone” = always from hypothalamus

“trophic hormone” = always from pituitary gland, causes
other glands to release hormones
- adrenal, ovaries, testes, thyroid, …
-
sexual maturation, sexual behavior, growth
of bones and soft tissue, water/salt balance,
metabolism, breast feeding…