History: The discovery of the
neuron
Galen
Lecture 1
Chapter 1 Overview
History and the neuron
Nerves were tubes, brain had holes (ventricles)
Spirits flowed through the tubes, much like fluid
Ramon y Cajal
Showed that nerve cells were separate individual
units and not networks of tubes
Noticed gaps between units
Noticed swellings (cell bodies)
Ramon y Cajal
History: The discovery of chemical
signals
Loewi
Loewi’
Loewi’s work
(1921)
Stimulated the vagus nerve in one heart to
slow it down
• Removed some of the fluid it was bathed in
• Added that removed fluid to a different heart
The second heart began to slow
Some chemical in the
fluid must be
working to slow the heart
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What is the nature of these
chemicals?
Hodgkin
and Katz (1949)
What did they find?
• Exp 1: When frog muscles are put into a solution
with low levels of sodium and chloride, they were
inexcitable
So either sodium or chloride in needed for excitation
• Exp 2: Replaced chloride in sea water solution with
sulphate and the nerve was still excitable
The Resting Potential
A difference between the voltage of the inside
and the outside of the neuron (approx -70mV)
Occurs because ions are found in different
amounts inside of the cell compared to outside
of the cell
The players:
Conclusion: sodium is at the root of the action potential
Starting levels of the main players
Two forces at work in a neuron
Electrostatic
gradient
SemiSemi-permeable membranes
Contain ion channels which open and close to
let certain ions in or out of the cell
Two types of channels
• Ligand gated channels
Opened by a change in voltage
More goes to less
The sodium potassium pump
Forces three sodium
ions out of the cell for
every two potassium ions brought back in
Opened by a chemical
• Voltage gated channels
ChargeChargeopposites attract
Diffusion
gradient
Why don’
don’t ions just move to where the
forces push them?
Sodium (Na+)
Potassium (K+)
Chloride (Cl
(Cl-)
Other Anions (A-)
Creates an imbalance between the inside and
the outside
The outside gets more sodium, which makes
it more positive
Takes up to 20% of a cell’
cell’s energy to keep
going
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In addition
Ion
channels are “leaky”
leaky”
Small amounts of ions get through even when
the channels are “closed”
closed”
This further contributes to the status of the resting
potential
The action potential
Ligand
gated channels play a large role
Opened by a chemical
• The chemical is usually a neurotransmitter
• Counteracted by the sodium potassium pump
Some chemicals increase the amount of
positive ions entering the cell
Others increase the amount of negative ions
entering the cell
EPSPs and IPSPs
If the
inside of the cell becomes more
positive, this is called an Excitatory
Postsynaptic Potential (EPSP)
If the inside of the cell becomes more
negative, this is called an Inhibitory
Postsynaptic Potential (IPSP)
Keys to the action potential
If
enough of an EPSP leads to the
surpassing of the threshold (approx 55mV), an action potential occurs
The increase in voltage inside the cell triggers
the opening of more and more voltage gated
sodium channels
These allow a LOT of sodium to enter the
neuron and increase the positive charge
inside the cell
Keys to the action potential
Around
+40 to +50mV, the sodium
channels close, leaving just the potassium
channels open
Potassium is now repelled to exit the neuron
by the positive charge inside (electrostatic
force) and by its concentration gradient
Too much potassium leaves and the cell
becomes hyperpolarized
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Refractory period
While the cell
is hyperpolarizing, it cannot
fire again (sodium channels are unable to
open)
Getting back to rest
Due
to the sodium potassium pump, the
resting potential is eventually restored and
the cell is ready to go again
Absolute refractory period
Once
the potassium has overshot the
resting potential (too much left), the cell
can rere-fire if it receives a larger than
average EPSP
“leaky”
leaky” channels aid in this process as well
Relative refractory period
Saltatory conduction
The axon terminal
The change in voltage in the axon terminal leads
to the opening of voltage gated calcium
channels
Let’
Let’s go through it again
slower…
slower…. Potassium Ions
The synapse
The
neurotransmitter crosses the synaptic
gap and binds to receptors on the
postsynaptic neuron
Calcium enters the cell
Calcium leads to exocytosisexocytosis- the neurotransmitter is
released into the synapse
The Resting Potential
Two forces at work in
a neuron
Force 1: Equilibrium:
the idea that the
concentration of a
molecule tries to
remain constant
throughout the
medium (substance)
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Status of the main players (ions)
Sodium
(Na+): more of it outside of the
neuron
(K+): more of it inside of the
neuron
Chloride (Cl
(Cl-): more of it outside of the
neuron
Potassium
Based on equilibrium…
equilibrium…
does Na+, K+, and Cl- want to do?
Are they “happy”
happy” where they are?
What direction will they move if allowed?
What
Due to equilibrium…
equilibrium…
Na+
wants to move inside the neuron
wants to move outside the neuron
Cl- wants to move inside the neuron
K+
How do charges react to each
other?
Opposites attract
Like
charges repel
What about charge?
Does
charge play a role in things?
According to charge, how might the ions
react?
One more piece to the puzzle
There
are large molecules inside the
neuron with negative charges
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Now which way do the ions want to
go?
Now which way do the ions want to
go?
Potassium:
Chloride:
Which way does equilibrium push?
What about the charge?
Now which way do the ions want to
go?
At rest
Resting
Sodium:
Which way does equilibrium push?
What about the charge?
Which way does equilibrium push?
What about the charge?
potential
-70mV
Potassium can cross the membrane
Sodium and Chloride cannot cross the
membrane
What will
potassium
want to do
at rest?
The action potential
Stimulation
When
stimulated by
another
neuron,
some Na+
channels are
opened
K+ channels
close
If the signal is
strong enough, it
makes it to the
axon hillock
If strong enough,
an action
potential is
generated
Threshold
Begins an action
potential
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The action potential
The action potential
At the beginning of the AP, Na
channels open and Na enters
the cell
Depolarization:
Now, there is more of a positive charge
inside than outside (the Na stops coming in
for the same reasons the K did originally, a
balance of two forces) this represents the
peak of the AP
occurs when Na+
flows into the cell
Due to Na+
channels
opening
How’
How’s potassium feeling now?
Sodium
moving
inside the cell
made the inside
of the cell more
positive
This repels
potassium to
move outside
The action potential
Conditions are now back where they
started in terms of potential and charge,
but the ions are in opposite positions
Called hyperpolarization
Then the Na/K pump brings the K back inside
the cell and the Na back outside the cell
The action potential
At the peak, K+
channels open and
K+ exits the cell
K+ channels open at the peak and K+ flows out
of the cell
This repolarizes the cell and even overshoots
the resting potential of before
2 K for every 3 Na
Uses energy (ATP)
The action potential
The Sodium
Potassium pump
restores the
original
environment of
the resting
potential so that
the neuron can
fire yet again
This is known as
the refractory
period
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Many different types of receptors
exist
Action of NTs at synapse
Receptors
can be either
single step or
multiple steps
Ionotropic:
Ionotropic:
single step
NT binds to
channels and
opens them
Can work
quickly: 2210ms
Metabotropic receptors
Multiple steps
NT binds to receptorreceptor- triggers G protein to bind
to ion channel and open it
The majority of receptors in the brain are
metabotropic
Slower than ionotropic receptors: 20ms –
10sec
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