Membrane Potentials and
Action Potentials
Chapter 5
And chapter 45
http://www.blackwellpublishing.com/matthews/default.html
1
Lecture outline
I. Review
A. Permeability
B. Concentration gradients
C. Sidedness of the membrane
II. Electrical gradients
A. Potential
B. Electrolytes
C. Conductance (permeability)
III. Resting membrane potential
A. Caused by
i. Proteins
ii. Na+/K+ ATPase
iii. K+ “leak” channels (pores)
B. Nernst potential
C. Why is RMP so close to K+ nernst potential
IV. Excitable cells
A. Gene expression of unique integral proteins
B. Neurophysiology terms
C. Action potentials
i. Caused by
a. passive diffusion of ions when channels open
Ligand gated
Voltage gated
2
• You don’t need to know the Nernst equation. I
will tell you how to think about it.
• You see body fluid compartments, separated by
a membrane.
• Will the solute diffuse down the concentration
gradient? Yes, if it can get through.
• Well, now I am adding that the solute also needs
to be able to go through an electrical gradient.
3
Cell Membranes
• What two conditions must be met for
diffusion of a species across a
semipermeable membrane?
– Is the membrane permeable to it?
– Does it have a concentration
gradient?
• If the answer is yes to both questions,
then the species will diffuse (Which
way? Down it’s gradient)
4
“Sidedness” of the membrane and some reasons why
Different permeability
Pumps
Protein channels
Remember to ask:
Is there a gradient?
Can it diffuse?
If allowed to diffuse,
which way would it
go?
inside
outside
(in mM)
(in mM)
Na+
K+
Mg2+
Ca2+
H+
HCO3ClSO42PO3-
14
140
0.5
10-4
(pH 7.2)
10
5-15
2
75
protein
40
142
4
1-2
1-2
(pH 7.4)
28
110
1
4
5
5
Not just separation of solutes, but
charges, too!
+
+
+
+
_ _ _ _
_ _ _ _
_ _ _ _
+
+
+
+
+
+
+
+
– Abundance of
negatively charged
proteins
– Na+/K+ ATPase (net
loss of positive
charges~ 4mV)
– Membrane is 100x
more permeable
(“leaky”) to K+
+
+
+
+
• Inside of the cell is
negative due to :
Let’s explore this concept more........ 6
Sidedness
• “Sidedness” of the membrane
• Sidedness means that the electrical charges on one side of the
membrane (positive or negative) are different than on the other side.
•
• Why does sidedness exist?
• Different permeability
• Pumps
• Protein channels
•
• How does a membrane become sided?
• Primary and secondary active transport, or pores that allow only one
particular solute to move. These things make a higher concentration
on one side. Therefore, sidedness is caused by proteins.
7
•
•
•
•
Take an electrode, pierce the membrane, attach to voltometer, compares
the charges inside and outside of the cell. Inside of cell is more negative
for three reasons:
Proteins are abundant inside cell, and are negatively charged at your
normal pH.
Sodium-potassium-ATPase mechanism contributes toward the
electronegativity inside the cell. Two K are pulled in while 3 Na go out. They
are all +1, so net loss of one positive charge, so the inside is more negative
than the outside.
Most important reason: potassium leak channels. If men are K and
women are Na, ladies are most abundant outside of cell, more guys inside
room. After class, guys want to leave, they can use the door. Ladies want to
get into the room, but to get in, they have to come under the crack of the
door. Not likely to get in. Sodium does not have leak channels, which are
created by integral proteins. Potassium leaves by leak channels,
contributing to negativity.
8
• How negative is the inside of the cell?
• Minus 70 mV (milivolts), depends on the cell. Heart cells
are minus 90, some are minus 50-60.
•
• We have chemical and electrical sidedness on a cell
membrane. The membrane has membrane potential
(separation of charges). You can calculate voltage. If
the charges on a battery reach equilibrium on both sides,
the battery will be dead. That can happen to our cells,
too. We need to use the electrical energy in our cells to
do kinetic work. You have to turn on a machine to
engage its electrodes. The cells don’t all allow the
9
diffusion of electrical current to do work with.
• The ones that can increase resistance have something
special that other cells don’t have. Cells that can
increase resistance have proteins that create
channels. Examples of this type of cell are neurons and
muscle cells; they allow charges to move across the
membrane, because they express genes that make the
integral proteins that create these channels. Charged
ions, K+, Na+, Ca++ are ions, so they are called
electrolytes. When they move, they carry an electrical
charge. What do electricians use to reduce resistance of
wires? They use Insulation, in the form of plastic coating
on wires. We need resistance (block flow of charges). A
cell creates this resistance by blocking the channel.
10
• Myelinated neurons carry current faster (the current skips over
the Nodes of Ranvier and just has to travel down the bare portions
of the axon). Another thing that affects speed of electrical
transmission is the size of neuron: bigger neurons carry current
faster (expand the freeway to add extra lanes, you will get home
faster).
•
• Conductivity means the permeability. If conductivity increases, it
means that permeability increased.
• Ions diffuse at a faster rate when there is less resistance. The more
resistance there is, the less conductivity, and less resistance will
cause more conductivity. Myelin reduces resistance because it
makes electrical charges move faster.
11
----
+
+
+
+
+
-
Electricity
• Current: the flow of charge
+
• Voltage: separation of opposite charges (mV)
– Voltage
What are the charged
– Voltage difference
things that run through our
– Potential difference
body fluids? Electrolytes!
– Potential
ions: Na+ K+
Cl- Ca++
• Resistance: opposition to charge
movement (friction)
• Conductance: allowing a charge to
move (permeability)
12
When dealing with things that are charged ….
You must ask an additional question!
1. Is the membrane permeable to it?
2. Is there a chemical gradient for it?
–
3.
Things tend to move from high to low
concentration
----
+
+
+
+
+
Is there an electrical gradient for it?
–
Things tend to move to regions of
opposite charge
+
Only then, can you predict!
•
How do you measure each of these
gradients or forces?
Sometimes, the chemical gradient is
favors one ion to go in one direction, and
the electrical gradient favors it to go in the
other direction. The stronger pull will win.
-
= Na+
13
• Every cell has a separation of charge; the
#1 reason is the leakiness of K. It leaks
out all the time, and the Na pushes K back
in. We use this electricity to do work.
Blood pressure, peristalsis of intestines,
muscles, etc, use this electricity for work.
14
Because of this separation of chemicals and
electrical charges, every cell has a Resting
Membrane “Potential”
• A difference in electrical charge
across the membrane (a potential
difference)
• More negative inside; more positive
outside
• Our cells are like batteries and some
cells can tap into this “potential
energy” to do work (“kinetic energy”)
• What generates it?
– Mainly, ion concentration gradients and
differences in membrane permeability
(leaky to K+ but not to protein)
• -70-90mV
15
• Why is the resting membrane potential
negative? Because K has leakiness, so it
escapes with its positive charge, leaving the
inside of the cell more negative.
• Which force is “winning” at rest? Potassium
• How can simple diffusion cause this potential?
There is not much Na inside the cell, so sodium
wants to diffuse in with its positive charge.
16
• The inside of the cell is negative because there are K leak channels,
that means there is greater permeability for K, so it will diffuse out of
the cell down its concentration gradient.
• The membrane potential (how negative or positive is) is a
number that is a reflection of the ion with the greatest
permeability. If our cells are minus 70 mV, it’s because they are
most permeable to K. Therefore, K will diffuse out its
concentration gradient, taking its positive charges with it,
leaving the inside of the cell more negative. What if the cell was
more permeable to Na? Sodium would diffuse down its
concentration gradient to the inside of the cell, taking its
positive charges with it, making the inside of the cell more
positive.
17
Membranes are leaky!
Cl-
Solutes diffuse down
their EC gradients.
Most leaky to K+
Not permeable to
proteins (too big!)
What happens?
“Diffusion potential”
Na+
Na+ Cl
Na+
Cl-
Na+
Cl-
Na+
Na+
K+
ClNa+
-
K+ K+
K+ K+ K+
- Proteins - Organic
- - Na
phosphates
Cl
-
+
-
Na+
Cl-
Let’s explore this concept more........
K+
18
So, we have a battle: diffusion of a chemical gradient
and the diffusion of the charges (Electrical potential )
+
-
- - - - -- - -- -- - - - +-- When will the
- - - -- negatively charged
-- - - - molecules stop
-entering the cell?
- -
The Nernst potential (equilibrium potential) is the theoretical
intracellular electrical potential that would be equal in magnitude but
opposite in direction to the concentration force.
In other words: when does the attraction between opposite charges
oppose the diffusion of a chemical gradient?
19
•
In the previous picture, just look at the number of blue-dot particles (ignore
the charges). There are more blue dots outside of the cell, so there is a
chemical gradient for the blue dots to move inside of the cells. Insert a
voltage rod to inject positive charges into the cell. The negative charge of
the blue dots will want to enter the cell because they are attracted to the
positive charges there. Thus, there are two reasons why these blue dots will
quickly enter the cell. But when will the blue dots stop going into the cell?
They will be attracted to the positive charge, but if they are all inside, the
chemical concentration gradient makes them want to diffuse out of the cell.
When the electrical and chemical gradient is equally powerful (in opposite
directions), that is the Nernst potential: No net gain or loss. Cells with
resting membrane potential are at minus 70mV. They are not at their
resting K potential. If you open more K channels than just the leak
channels, there will be more movement of K out of the cell, and the potential
will get closer to minus 94 mV (at which time, the cell will reach equilibrium,
and the cell will die; but the body does not let it get that far).
20
• The Nernst potential (equilibrium potential) is the
theoretical intracellular electrical potential that would be
equal in magnitude but opposite in direction to the
concentration force.
• In other words: when does the attraction between
opposite charges oppose the diffusion of a chemical
gradient?
• In this case we’re changing the electrical potential across
the membrane to see what happens to the concentration
gradient of the ion. In reality, the concentration gradient
is changed during various cellular processes which
21
determine the Nernst potential.
Membrane Potential (Vm):
- charge difference across the membrane -
inside
+
K
Na+
outside
K+
+
Na
…how can passive
diffusion of
potassium lead to
development of
negative
membrane
potential?
Answer: Potassium leaks out of
the cell, taking its positive
charge with it, leaving the inside
of the cell more negative. 22
Simplest Case Scenario:
inside
outside
If a membrane were permeable
to only K+ then…
+
K
K+
K+ would diffuse down its
concentration gradient until the
electrical potential across the
membrane countered diffusion.
23
• As K leaves the cell, it takes a positive charge outside
with it, so the inside is more negative. However, as the
inside of the cell is becoming more negative, the outside
of the cell is becoming more positive, and the positive
charges will want to flow back inside of the cell since
they are attracted to the negative charges. This is
electrical potential that counters the net diffusion of K.
• The electrical potential that counters net diffusion of
K+ is called the K+ equilibrium potential (EK).
• The equilibrium potential of K is minus 94 mV
• So, if the membrane were permeable only to K+, Vm
would be -94 mV (cell death from equilibrium)
24
Simplest Case Scenario:
inside
outside
If a membrane were permeable
to only K+ then…
+
K
K+
The electrical potential that
counters net diffusion of K+ is
called the K+ equilibrium potential
(EK).
So, if the membrane were permeable only
to K+, Vm would be -94 mV
25
Simplest Case Scenario:
If a membrane were permeable
to only Na+ then…
Na+ would diffuse down its
concentration gradient until potential
across the membrane countered
diffusion.
inside
Na+
outside
+
Na
The electrical potential that counters
net diffusion of Na+ is called the Na+
equilibrium potential (ENa).
So, if the membrane were permeable only
to Na+, Vm would be +61 mV
26
• But the body prevents the cell from reaching equilibrium.
Since the resting membrane potential is minus 70 mV,
(a negative number), it tells us that potassium has the
greatest membrane potential at rest. Don’t confuse this
with thinking that potassium has a negative charge. It
has a +1 charge, the same as sodium. But when
potassium leaves the inside of the cell, it takes its
positive charge with it, leaving the inside of the cell more
negative. The inside of the cell is negative because
proteins have a negative charge, and the cell contains so
many proteins.
27
•
•
•
•
•
•
•
•
•
•
At resting membrane potential, cell voltage is at minus 70 mV.
Since potassium’s chemical equilibrium is minus 94, potassium’s chemical
equilibrium is not met yet.
That means that it will WANT to flow out of the cell.
But the difference between the voltage of where it is (minus 70) and where it
wants to be (minus 94), is only 24 mV.
This is not a very strong difference.
Since sodium’s chemical equilibrium is plus 61 mV, sodium’s chemical
equilibrium is not met yet.
That means that it will WANT to flow into of the cell.
The difference between the voltage of where it is (minus 70) and where it
wants to be (plus 61), is 131 mV.
This is a much stronger difference, compared to potassium. Therefore, the
ion with the strongest driving force is sodium because its equilibrium
potential is much different from the resting membrane potential.
If you want to harness the electrical current to use it to do work, use the
sodium driving force instead of potassium.
28
Anatomy of a neuron
29
•
•
Receptors on the dendrites act to bind proteins, can direct things into and
out of the cells.
Neurotransmitters from one synaptic knob are released onto another
dendrite; a channel opens within the receptor on the dendrite. If the channel
was for sodium only, sodium will move inside of the cell. The sodium travels
down to the axon hillock. If enough sodium is allowed to enter the soma,
the sodium that reaches the axon hillock can trigger the opening of
the first voltage-regulated gated channel on the axon. Channels distal to
the hillock are locked down (bound), and will open only if electrical charges
have been reduced on inside of cell (they are voltage regulated). As the
sodium gets to the axon hillock, the axon will get less negative, so the
inside of the cell is less negative, will it will open K voltage channels.
The first opened gated channel will open the next gated channel, and so on,
down the axon. The axon hillock is the trigger zone where you start to
see voltage gated channels.
30
• When you are firing a gun, even if you squeeze the
trigger slowly, there is a trigger point where the bullet will
fly out of the gun. Pulling the trigger slow or fast does not
change velocity of the bullet. The voltage gated channels
are same; if one opens, they will all open one by one,
like a wave. If enough sodium diffused in when a ligand
channel opened, the first voltage gated channel will
open. A ligand is an integral protein in a cell
membrane that binds to a chemical, and then
transports it into the cell. Thus, it serves as both a
receptor and the transporter.
31
• If you want more electrical current, open the
sodium channels first (instead of the
potassium channels). When you increase
sodium conductance (permeability), sodium can
move down its electrical gradient as well as its
chemical gradient. Sodium’s equilibrium
potential (+61), will make inside of the cell
very positive, which is the opposite of the
resting membrane potential (minus 70). The
reversal of the membrane potential is called
the ACTION POTENTIAL.
32
• But you cannot let sodium continue on into the cell until it reaches
equilibrium, or the cell will not be able to metabolize, and it will die.
To prevent too much sodium from entering the cell, you have to
open the K channel to allow K to diffuse out by its chemical and
electrical gradients. This is called the dance of the gates.
During an action potential, the sodium gate opens first, the
potassium gate opens second. Are the ions where they should
be? If not, something needs to push K back into the cell and Na
out: Na-K ATPase (the mother protein, or housekeeping
protein). Mom organizes the house and the kids mess it up again.
She directs the kids to take their toys and put that here, and put that
there. During action or resting potential, Na-K ATPase is active
all the time, constantly trying to reestablish the gradients. She
never stops working. When is the Na-K ATPase active? ALWAYS!
33
Why is Vm so close to EK?
Ans. The membrane is far more permeable to K+ than Na+.
Normal conditions
EK -94
Vm -74
ENa+61
0
mV
20 mV
135 mV
What is the net driving force on K+ ions?
What is the net driving force on Na+ ions?
Which way do the ions diffuse?
What effect does increasing Na+ or K+
permeability (or extracellular concn) have on Vm?
The resting membrane
potential is closest to
the equilibrium
potential for the ion
with the highest
permeability!
34
What keeps the ion gradients from running down? The
sodium/potassium ATPase (“the housekeeper”)
Do we want our cells to be like a “dead battery?”
inside
+
K
Na+
outside
+
Na
ATP
K+
3 Na+
ADP
Integral membrane protein found in
all cells which “pumps” (against
their gradients across the
membrane) Na and K.
Fueled by ATP
ATP
ADP + Pi + energy
2 K+
Remember: sodium is
pumped out of the cell,
potassium is pumped in...
This pump is electrogenic, it
contributes slightly to RMP
35
The “Resting” Cell
ClNa+
Na+
Cl-
Na+
ClThe
+
Housekeeper Na
Na+
Cl-
Na+
Cl-
K+
Na+ Na+
Diffusion, leak
+
K+ K+ Na
K+ K+ K+
- Proteins
-Organic
- - Na
K+
phosphates Cl
-
+
+
+
-+
K+
-
Na+
Cl-
Diffusion, leak
K+
Cl36
• Integral membrane proteins found in all
cells will “pump” (against their gradients
across the membrane) Na and K. This is
fueled by ATP.
• ATP  ADP + Pi + energy
37
http://bcs.whfreeman.com/thelifewire/content/chp44/4402001.html
http://www.sumanasinc.com/webcontent/animations/biology.html
38
What if…..
• What if a membrane suddenly became
MORE PERMEABLE to Na+?????
+
• Even for just a moment in time…..
Na
Cl
• What would Na+ do? (Ask yourself the
3 questions)
Na Cl
Cl-
Na Cl
+
+
Which way is the electrochemical
+
gradient for Na+?
Na
Cl
Electrical: inward
Na Cl
Chemical: inward
+
Answer:
Most definitely INWARD
Sodium WANTS IN!
Na+
++
++
--Na+
Cl-
-70 mV
What would happen to the membrane potential of
the cell when this event occurs?
39
• What would happen to the membrane
potential of the cell when you open up
a sodium channel?
• If we instantly increase sodium
permeability, sodium will enter the cell,
creating a large electoral current, then
K permeability will increase, and the
membrane potential will return to
negative.
40
• Excitable cells (neurons and muscles) are those
that want this large electrical current to use for
work.
• They have proteins that are sodium channels.
Not all cells have these proteins. All cells have
the genes to make these proteins, but only the
excitable cells EXPRESS these genes, and
actually make the proteins that fuse with the
cell membrane and form a sodium channel.
Muscle cells use the electrical force to contract,
and neurons use it to excite the neurons
41
touching them.
Excitable Cells
• Cells that can experience a momentary change
in membrane voltage are “excitable” cells
• That temporary change in voltage is due to a
momentary change in permeability
• The membrane, for only a moment, becomes
more permeable to Na+ than to K+
• When it’s called an Action Potential-it is a
reversal of the membrane potential!
• Cell becomes positive inside!!!
• Question: What can allow membrane
EXPRESSION !
permeability to these ions?
• Why are neuronal cells and muscle cells able to
change their membrane potential?
Integral proteins that can open and close depending on stimulus
How did we discover these unique integral proteins?
42
Hodgkin-Huxley Expts, 1952
Squid Giant Axon
Few neurons, large diameter
Large enough to insert microelectrodes
Stimulating microelectrodes (inject current) to disturb cell with electrical
stimuli
Recording microelectrodes (see current changes in cell and record them)
43
http://www.science.smith.edu/departments/NeuroSci/courses/bio330/squid.html
Definitions:
• There is a potential difference (pd) across
the cell membrane
• (minus 70 mV) is called the “Resting
Membrane Potential”
• Because a charge is present (it is not
zero), we say the membrane is
“polarized”
44
• If it becomes less negative, it is called depolarization
(happens when sodium is entering the cell).
• If it becomes more negative than minus 70, it is
hyperpolarization. (happens when K leaves the cell)
• In either case, when you go back towards minus 70,
it is repolarization.
• Threshold is the point at which the first voltageregulated sodium channel opens.
Question
• To depolarize a cell, what kind of charge must be put
into the cell, positive or negative? Positive
45
----
+
-
70 mV
Voltmeter
0 mV
repolarization
“Resting Membrane Potential”(70 mV)
-90 mV
excitability
threshold
depolarization
hyperpolarization
excitability
Depolarization-a current entering the cell that decreases the
polarity (voltage) across the membrane (that is, bring voltage
closer to 0 mV).
To depol, what kind of charge must be put into the cell, positive
or negative?
Hyperpolarization-a current that increases the voltage across the
membrane (brings it farther from 0 mV.)
repolarization
towards resting potential
+
resting
potential
-
46
• When you take the mantle off the giant squid,
the nerves are right there, and are so big, you
can touch them. Hodgekin and Huxley put one
of these neurons in an isosmotic solution and
inserted four wires along the axon, distal to the
hillock. The first wire was attached to an
instrument that can inject a positive charge into
the cell (increasing its membrane potential). The
next three wires (R1, R2, R3) received the signal
and measured the resulting charge. In this way,
they could find out if the injected positive charge
would continue down the axon or dissipate.
47
• With a small injection of a positive charge, they found the membrane
potential was less as it got farther from electrode (the charge
dissipated). Then, they put in a lot more positive charges, there was
a greater potential in the other three receiving electrodes, but it still
dissipated. Then they gave it a whopping positive charge, RMP rose
to minus 160, and they found a reproducible membrane potential,
which continued through length of axon, and they were able to
maintain this reversal of the RMP. The voltage gated sodium
channels allowed the Na to come in, allowed more Na gated
channels to open, one after another. This is called an action
potential. Sodium ions entering the cell is what created the
action potential. You can have hundreds of thousands of action
potentials in a second, but there is not a flood of sodium coming in;
only a few ions need to go in to make an action potential.
48
Voltage
(mV)
First try: a small depolarizing
+40 stimulus (-65 mV)
+30 +20 +10 0 -10 -20 -30 -40 -50 -60 -70 time
Stim
Elec
++++
REC 1
+++
REC 2
++
REC 3
+
49
Voltage
(mV)
Next try: a slightly larger
+40 depolarizing stimulus (-60 mV)
+30 +20 +10 0 -10 -20 -30 -40 -50 -60 -70 time
Stim
Elec
++++++
REC 1
++++++
REC 2
+++
REC 3
++
50
Next try: a slightly larger depolarizing stimulus (-55 mV)
+40 Action
+30 Potentials
+20 +10 0 Local
-10
Voltage
Potentials
(mV) -20 -30 RMP -40 -50 -60 -70 time
Stim
Elec
REC 1
REC 2
REC 3
+++++++++++++++++++++++++++ +++++++++
51
Can we get even larger
Action Potentials?
+40 +30 +20 +10 0 Local
-10
Voltage
Potentials
(mV) -20 -30 RMP -40 -50 -60 -70 Stim
Elec
Try an even larger depolarizing
stimulus (-50 mV)
Action
Potentials
time
REC 1
REC 2
REC 3
----52
Can we get even larger
Action Potentials?
+40 +30 +20 +10 0 Local
-10
Voltage
Potentials
(mV) -20 -30 RMP -40 -50 -60 -70 Stim
Elec
Try an even larger depolarizing
stimulus (-50 mV)
Action
Potentials
No
higher, no
larger,
Identical!
time
REC 1
REC 2
REC 3
----53
Definition:
Threshold voltage is
the minimum voltage
needed to trigger an
AP. not a number, rather
the “trigger” to open
voltage operated
channels
Note the
timeframe for one
54
AP
Compare LP to AP
Local Potentials
Action Potentials
• They don’t reflect the shape,
• Generally, they reflect
size of the stimulus, rather
shape, size of voltage
they are uniform in size,
stimulus (similar to
shape; always identical
stimulus pulse)
• They are “all-or-none” (ie.
either you trigger an AP if you
• They are graded in size
reach threshold – or if
(ie. bigger stimuli give
subthreshold, you don’t get
bigger depolarizations)
an AP – get local potential.)
• They “die out” (voltage • They do not diminish in size
grows smaller) as they
no matter how far from the
stimulus; regenerate anew at
move from site of
each point along the axon
stimulation
55
(resistance!)
Parts to an action potential:
• Upstroke: Na is more permeable, cell
becomes less negative
• Downstroke: K permeability is greater,
cell returns toward negative,
repolarization.
• Hyperpolarization: Dips below line
56
• As sodium channels open, it is recorded on a machine as an
upstroke.
• The peak of the curve shows that Na channels are deactivated, so K
channels open, recorded on the machine as a downstroke.
• Actually, sodium channels do not have just two positions (open or
closed); they have three gated properties, like a stop light: red,
yellow, green. If a light is green, you are conducted through
intersection. When the light is yellow, you should slow down and not
go through the intersection. Likewise, in the middle position, the
sodium voltage channel prohibits further sodium from crossing
the channel.
57
• Yellow lights do not turn green. It has to turn red
first. There are 2 amino acid lids (gates); an external
and internal gate. Together, they are shaped like a ball
and chain. When the voltage becomes positives, the
AA’s change their charge, and their ball and chain
will rock over and cover up the channel. This state
(yellow light) means inactivation. The amino acids
have to change their charge to move back out of the way
(red light), meaning deactivation. Then the channel
can become active again. It is a safely mechanism,
insuring that another neuron cannot fire another action
pot before it is ready to receive one.
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• When the gated channel is yellow, it is in absolute
refractory period. This means that it cannot go from
yellow to green. When enough channels are deactivated
(red light), they can open again. Then neuron can fire
again. After a man ejaculates, he needs some time (a
refractory period) before he can do it again! But he will
need to put more energy into to get erection than he did
the first time; needs more stimulus. Likewise, if you
need neurons to fire quickly, you need greater
stimulus.
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• Local potentials are graded. Need a greater stimulus for greater
potential.
• Action potentials are maintained, and every point on the neuron
shows the same amount of charge.
• The neuron that is responding to a small amount of tissue
damage will send fewer action potentials than a neuron that is
responding to a large amount of tissue damage, but the current
is the same. The brain knows from the greater number of action
potentials about the amount of damage; the frequency increases for
bigger cut. The current is the same for small or large cut: all or none,
like a stop sign, instead of a traffic light.
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Action Potentials
• They don’t reflect the shape, size of the
stimulus, rather they are uniform in size,
shape; always identical
• They are “all-or-none” (i.e. either you
trigger an AP if you reach threshold – or if
subthreshold, you don’t get an AP – get
local potential.)
• They do not diminish in size no matter
how far from the stimulus; regenerate
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anew at each point along the axon
What is responsible for the change in membrane
permeability during the action potential?
• Although called “action”potential, it
is NOT an active (energyconsuming) event for the cell. It
is purely a passive event. It is
due to diffusion of ions!
• It is dependent on
– ionic electrochemical
gradients (Na+, K+) and
– the membrane’s permeability.
Excitable cells have “fickle” cell
membranes…they keep changing
their permeabilities.
What determines the membrane’s
permeability at any moment?
Answer: GATED ion channels—
These allow SIMPLE DIFFUSION
of ions down their
electrochemical gradients
http://www.blackwellpublishing.com
/matthews/channel.html
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NEUROBIOLOGY Molecules, Cells and Systems
Gary G. Matthews
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Gated Ion Channels
1) Allow simple diffusion
2) Can open and close
3) Are selective
VGC (Voltage-gated channels): Open/close depending on the voltage
across the membrane
Na+ VGC, K+ VGC, Ca++VGC
Located on the axon, at hillock and beyond
LGC (Ligand-gated channels): are not dependent on membrane potential but binding
of ligands (e.g. neurotransmitters)
Neurotransmitter receptors
Located on dendrites and cell body, above hillock
in
Na+ and
Na+
ions
other
out
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http://icarus.med.utoronto.ca/neurons/index.swf
http://creativecommons.org/licenses/by-nc-nd/2.0/
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Ion channels cause the action potential
•
Thus, permeability of axon membrane to ions is
determined by the:
number of open channels
• Ion channels - structure
 proteins that span the membrane
 have water filled channel that runs through
protein
• Ion channel - properties
 Have conducting states (open) and nonconducting states
 Ion channels are usually selectively permeable
• some pass only Na ions and are generally called
‘Na channels’
• some pass only K ions = ‘K channels’
• some pass only Ca ions = ‘Ca channels’
(important in synaptic transmission)
• some pass only Cl ions = ‘Cl channels’
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• The occurrence of action potentials means
the gated channels are open. When they are
open, ATP is not used, it is simple diffusion.
But resting membrane potential requires ATP
to keep it at steady state. Homeostasis (steady
state) requires a lot of energy (ATP).
Homeostasis is the opposite of equilibrium. If
the cell voltage reaches minus 94, it is at
equilibrium, no driving force is present, cell
death.
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• Voltage gates open if there is membrane potential, or if
there is a ligand.
• A ligand is a type of protein in the cell membrane that
binds to a chemical and this binding causes a
conformational change (change in shape and position) of
the ligand, so that the channel opens.
• A ligand both a receptor and a channel. It allows sodium
to migrate into the cell. If it is enough, the first sodium
voltage gate opens, then the next, and the next.
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The graphs shows you:
•
•
•
•
•
•
•
Red is sodium conductance (permeability).
When it is greatest, compare it to the
membrane potential
Purple is the action potential (the current)
Blue is potassium conductance.
Green is sodium/K ratio. At time zero, this
ratio is 0.01, very low.
Before an action potential, Na permeability
is low.
K has 100x greater permeability than Na
during resting membrane potential.
As Na permeability increases, Na rises
to 1000x greater than K. Cell becomes
more positive. Then K channels become
activated, so K increases permeability, it
leaves cell, takes a long time to deactivate,
so you get hyperpolarization, and the inside
of cell becomes more negative. When
restored, the cell can fire an action potential
again.
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You need to understand all of this for your
homework. Let’s go over this again, with numbers:
• Resting membrane potential indicates which ion has
greater permeability: K has the greatest permeability.
• Let’s say there are 1000 K channels open, and sodium
only has 10 channels open.
• 10 divided by 1000 is 0.01, so K is 100x more permeable
than Na.
• During an action potential, threshold is reached, and Na
channels open, lots of them.
• Now the ratio is 10,000 Na channels open, and only 10 K
voltage gated channels open.
• Now ratio is 1000x in favor of sodium.
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• When membrane potential gets to +30, it reflects
the permeability of sodium, striving towards its
potential of +61, but it never gets there. The ball
and chain stops it. As sodium conductance is
declining, K is increasing, and membrane
potential goes back down toward a negative
value. This reflects the ion with greatest
permeability; in this case, it is K. It takes a while,
so you see a hyperpolarization, where there is
even greater K permeability than what you had
at resting membrane potential.
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