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9/23/16 - W3D4H3
Neurons and Action Potentials
Why This Topic?
Action potentials are the basic unit of signaling in the central nervous system
(CNS).
All information our brain receives about the sensory world, and likewise all the
sensations, emotions, thoughts and dreams generated in the brain, are conveyed via
action potentials.
Emergent properties are any unique property that "emerges" when component
objects are joined together in constraining relations to "construct" a higher-level
aggregate object, a novel property that unpredictably comes from a combination of
two simpler constituents
Learning Objectives
1. Explain the ionic basis of the action potential.
2. Explain the concept of threshold in terms of the underlying ion
channel activity.
3. Describe the refractory period and how it is produced mechanistically.
Next Week 9/27
4. Describe how changes in resting membrane potential affect the action potential.
5. Explain the propagation of an action potential down an axon and describe how
the refractory period contributes to this.
6. Describe the importance of myelination for action potential propagation.
A Quick Review
Ion gradients across the membrane are maintained by the Na+/K+ ATPase pump.
This protein pumps three Na+ ions out of the cell and two K+ ions into the cell helping maintain the necessary
concentrate gradients that we’ve studied earlier.
+
Na+ Na+
Na
Establishing these gradients is a way to store POTENTIAL ENERGY that
can be used to do work, which is a prerequisite for cell survival and cell
function.
For example, the concentration differences for Na+ can be used to send
electrical signals (i.e., action potentials) and also in secondary active
transport to move glucose and calcium against their concentration gradients.
(i.e., concentrate glucose in the cell (via Na+/Glu symport) or to pump Ca2+
out of the cytosol (via Na+/Ca2+ antiport).
K+ +
K
A Quick Review
Recall that the Nernst equation can be used to describe the behavior (i.e., movement) of the
four most relevant ions: Na+, K+, Cl- and Ca2+
Review: Using these values in Table 1, can you calculate the equilibrium potentials for these ions
at body temperature using the Nernst equation?
Table 1. Normal resting concentration of various ions
Ion
[Intracellular]
(mM)
[Extracellular]
(mM)
Nernst Equilibrium
Potential (mV)
Na+
12
142
66
K+
140
4
-95
Cl-
8
105
-69
Ca2+
7.0 x 10-5
2.5
139
*mM = mmol/L
Nernst equilibrium potential (mV) is:
EqX = (61.5/z) Log ([Xout]/[Xin])
A Quick Review
 If the membrane is permeable to a single ion, the membrane potential will move
towards and reach the equilibrium potential for that ion. For example:
o if the membrane were only permeable to K+, then the resting membrane potential
would equilibrate at -95 mV.
o if the membrane were only permeable to Na+, then the resting membrane
potential would equilibrate at +66 mV.
o If multiple ions are permeable to varying extents this results in what?
 A resting membrane potential that is not equal to any one of the calculated
Nernst potentials.
o A typical membrane potential lies between -65 mV and -70 mV. What ions do you
think are the most permeable?
 Changing the membrane potential does not require the movement of very many ions.
For example, only 1 in every 100,000 K+ ions needs to move to change the membrane
potential 1 mV.
LO1: Ionic basis of the action potential:
PNa and PK are the permeabilities for sodium and potassium, respectively.
Knowing the basis of ion distribution and movement across the plasma membrane Hodgkin and Huxley (1939) able to explain
the action potential by measuring flow of current across the membrane, shown below.
During an action potential (AP) the membrane potential (V) briefly reverses, hyperpolarizes and then returns to
baseline.
This correlates with an increase in sodium conductance followed by an increase in potassium conductance. This
was a major discovery using the “patch clamp” technique.
Action Potential
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (1 of 9)
Action Potential
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (2 of 9)
Action Potential
“rising phase” of the AP
(depolarizing)
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (3 of 9)
Action Potential
“steep rising phase” of the AP (depolarizing)
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (4 of 9)
Action Potential
“overshoot”
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (5 of 9)
Action Potential
“falling phase” of the AP
(repolarizing)
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (6 of 9)
Action Potential
“undershoot” (hyperpolarization)
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (7 of 9)
Action Potential
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (8 of 9)
Action Potential
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (9 of 9)
Action Potential
permeability
permeability
From: Silverthorn, D.E. Human physiology: an integrated approach (7th edition). New Jersey: Prentice
Hall/Pearson. 2016.
Figure 8-9 (bottom)
Voltage-gated Na+ Channels
Figure 8-10a
Voltage-gated Na+ Channels
Figure 8-10b
Voltage-gated Na+ Channels
Figure 8-10c
Voltage-gated Na+ Channels
Figure 8-10d
Voltage-gated Na+ Channels
This repolarization is caused by
voltage-dependent K+ channels
opening.
Figure 8-10e
The Hodgkin cycle
Figure 8-10e
LO1: Ionic basis of the action potential:
PNa and PK are the permeabilities for sodium and potassium, respectively.
http://tmedweb.tulane.edu/pharmwiki/doku.php/introdu
ction_to_cardiac_physiology_electrophysiology
LO2. Explain the concept of threshold in terms of the underlying ion channel activity.
If we inject a weak, brief depolarizing current
(inward movement of positive charge) into an
excitable cell, we will see voltage changes that scale
with the magnitude of the current that we inject
(Figure 1).
If we gradually increase the magnitude of the
injected current, at some point something very
different happens: the membrane voltage makes a
large and rapid excursion in response to injected
current. This is an action potential: a large, rapid
and discrete change in transmembrane voltage.
Action potentials are the basic unit of signaling in
the central nervous system. All the information
our brain receives about the sensory world, and
likewise all the thoughts and dreams generated in
the brain, are conveyed via action potentials
The “Threshold”
Hodgkin and Huxley were able to stimulate APs with small depolarizing pulses
They found a depolarizing pulse of about 5 mV would result in an action potential 50 %
of the time and defined this degree of depolarization threshold, that is a degree of
depolarization the resulted in a Hodgkin-Huxley cycle half of the time.
A stimulation less then this is less then 50 % likely to result in an AP while a greater
stimulus is more likely to give rise to an AP
Once an AP is initiated though, it is an all or none phenomenon. There are no half Aps.
LO 3. Describe the refractory period and how it is produced mechanistically
There is a theoretical maximum frequency at which APs can fire. This is
because the AP is an all or none phenomenon (and you cannot trigger
another AP in the middle of the upslope of a Hodgkin-Huxley cycle) and
because h-gates will have to be reset before they sodium channels can
reopen and initiate a new action potential.
This period is called the refractory period and can be divided into:
• The absolute refractory period when h-gates are shut and you
cannot trigger a new AP until they are open.
• The relative refractory period when some h-gates are shut and the
cell is hyperpolarized an AP can be triggered but it will require more
input and not be as rapid as a normal AP.
A Quick Review
LO1: Ionic basis of the action potential:
LO2. Explain the concept of threshold in terms of the underlying ion channel activity.
If we inject a weak, brief depolarizing current
(inward movement of positive charge) into an
excitable cell, we will see voltage changes that scale
with the magnitude of the current that we inject
(Figure 1).
If we gradually increase the magnitude of the
injected current, at some point something very
different happens: the membrane voltage makes a
large and rapid excursion in response to injected
current. This is an action potential: a large, rapid
and discrete change in transmembrane voltage.
Action potentials are the basic unit of signaling in
the central nervous system. All the information
our brain receives about the sensory world, and
likewise all the thoughts and dreams generated in
the brain, are conveyed via action potentials
LO 3. Describe the refractory period and how it is produced mechanistically
A few words about conductance.
The movement of ions across the membrane is described by conductance, which is the inverse of resistance as represented
by Ohm’s law:
I = V/R
where I is current, V is voltage which is the driving force, and R is resistance.
Conductance of current is equal to the inverse of resistance. The conductance is a direct function of the number of
channels that open and allow electrical current carried by one or more ions to flow into or out of the cell.
R = V/I
or
Conductance (G) = I/V
So, conductance for Na+ is:
GNa+ = INa+/VNa+
Where V is = Vm-ENa+
Do you get this?
NOTE: The SI unit of measure for R is the ohm (Ω), for current (I) it is the amp (A), for voltage (V) it is the volt
(V) and for conductance (G) it is the siemens (S).
A few words about the reversal potential.
Remember, conductance for Na+ can be calculated as:
GNa+ = INa+/VNa+
Where: VNa+ is = Vm-ENa+
then substituting:
GNa+ = INa+/(Vm-ENa+)
And finally, rearranging to solve for current due to sodium flow we have:
INa+ = GNa+(Vm-ENa+)
1. So, if all the Na+ channels are closed, GNa+ = ? What then is INa+ ?
2. Or, if channels are open but Vm = ENa+ , what is the driving force and what is INa+ ?
The Vm at which no flow occurs for Na+ is called the reversal potential, and in this case = ENa+
3. What will happen Vm is LESS than ENa+? (e.g., Vm = -70 mV)
4. What will happen if Vm is GREATER thanENa+? (e.g., +80 mV)
What if the reversal potential for an ion channel that is selective for “univalent”
cations so both Na+ and K+ are permeable? (e.g., the Ach muscarinic receptor in the
motor end plate of skeletal muscle.)
• If ACh were to open an ion channel permeable only to K+, then the reversal
potential of the end plate would be at the equilibrium potential for K+, which for a
muscle cell is close to -100 mV. (Would K+ flow? No)
• If the ACh-activated channels were permeable only to Na+, then the reversal
potential of the current would be approximately +70 mV, the Na+ equilibrium
potential of muscle cells. (Would Na+ flow? YES!!!!!)
• If these ACh-activated channels were permeable to both Na+ and K+, then the
reversal potential of the end plate would be between +70 mV and -100 mV.
• IN this case, the reversal potential is NOT equal to either EK+ or ENa+.
• What actually happens in realty?
A Quick Review
The resting membrane potential is largely set by outward leakage of potassium, however, some
inflow of sodium occurs through sodium channels.
The relative degree of sodium influx can influence the resting membrane potential (RMP)
Neglecting the role of Cl-, which of these cell types do you believe has the lowest
permeability to sodium?
Note, for the moment we are neglecting the role of chloride movement. Some cell types are freely permeable to
chloride (through open channels) while others have gated chloride channels that can be opened and closed. So, be
prepared in the future to consider this when discussing specific cells and tissues.
Based on your review of Nernst E(Cl-) values, what influence will movement of chloride have on the membrane
potential? (Assume EqCl- = -69 mV).
How would calcium movement influence RMP? (Hint: based on what you know about typical Ca2+ concentrations,
what direction will Ca2+ flow ?)