SI October 13, 2009
Resting Membrane Potential
Glossary of Terms and Useful Info
Efflux: Flow of ions out of the cell
Influx: Flow of ions into the cell
Resting EM: Resting Membrane Potential: -70mV
Eion: Ionic Equilibrium Potential for a given ion. AKA the value of the membrane
potential if cell is only permeable to the given ion. Based on:
1)Concentration Gradient IN vs. OUT of given ion
2)Electrical Gradient
EK: Ionic Equilibrium Potential for K+: approx -90mV
ENa: approx +66mV
ECl: approx -42mV
Voltage/Potential: Measure of the charge difference across a membrane
(IN with respect to OUT)
Permeability: Extent to which certain ions can flow across a membrane
→ Dictated by how many channels are open for that ion
Depolarization: Membrane potential becomes closer to zero (less negative)
Hyperpolarization: Membrane potential becomes farther from zero
“[ ]”: the symbol/abbreviation for concentration. Example:
Under typical conditions [K+] IN >>>>> [K+] OUT
Warm Up:
What are three important properties of ion channels
1) PASSIVITY: Ion channels are passive since they are not transporting or pumping material; they
rely on diffusion of ions along gradients. Once an ion channel is open, whether or not ions flow is
determined by the electrical and chemical forces operating on the ion, which are generated
independently of the channel itself.
2) SELECTIVITY: Ion channels have pore loops/ selectivity filters that can either select generally
anions vs. cations, or more specifically: cation A vs. cation B. For example, potassium channels (leak
and delayed rectifier) demonstrate the exquisitely fine-tuned selectivity that ion channels can
achieve: they permit passage of Potassium (monavelent cation, weight = 39 atomic mass units, radius
= 227 * 10-12 meters) and deny passage of Sodium (monovalent cation, weight = 23 atomic mass units,
radius = 186 * 10-12 meters). The charges are the same, the radii differ by 41 millionths of a
millimeter, and the weights differ by 16 millionths of a billionth of a billionth of a gram, and the
channel can tell them apart!
3) REGULATABILITY (my word): Besides leak channels (whose activity can only be regulated
essentially through inserting or removing them from the membrane) ion channels are subject to
exquisite regulation. Regulation (“gating”) is accomplished in the three manners discussed below.
What is the major ATP consumer of the Central Nervous System? What is the net effect of its activity?
The Sodium / Potassium Pump (AKA the Na + / K+ ATPase)
Per cycle it pumps 3 Sodium Ions OUT and 2 Potassium Ions IN.
As a consequence, it balances that activity of the leak channels for these ions, thus maintaining their
concentration gradients. Also, since 3+ goes out and 2+ goes in, each cyle removes a net 1+ charge
from the cell, thus helping to restore RMP following depolarization.
What are the four different functional types of ion channels?
1) Leak Channels. Associated with maintenance of Resting Membrane Potential.
Once present in the membrane, leak channels are essentially always open. They possess the
properties listed above, though regulation is generally accomplished through insertion/removal.
2) Mechanically Gated Channels. Associated with generation of Graded Potentials.
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Resting Membrane Potential
Designed in such a way that mechanically distortion of the membrane through vibration or
stretching causes the channel to open. Basis for hearing, touch, pressure, proprioception.
3) Chemically Gated Channels. Associated with generation of Graded Potentials.
This type of ion channel has receptors built in for signaling chemicals that can open or inhibit
opening of the channel. They respond to two major categories of signaling molecules:
Neurotransmitters, and Intracellular metabolites/signaling molecules.
4) Voltage Gated Channels. Associated with generation/propagation of Action Potentials.
What is an electrochemical gradient?
Term that expresses the sum of the 2 forces operating on a charged molecule or ion in order to
indicate the net direction of diffusion.
1) Chemical: Net flow from areas of high concentration to areas of low concentration.
2) Electrical: Charged molecules and ions flow towards regions of the opposite charge
What is the significance of Ohm’s law as we have learned it?
V = IR
Voltage = Current * Resistance
Resistance of plasma membranes is HIGH (lipid core prevents simple diffusion of charged
molecules/ions). So R is a very big value. Thus very small changes in ion flow (current) result in huge
changes in voltage measured across the membrane. That’s all you need to know.
Exercises:
Outline in your notes the conditions that create a resting membrane potential
1. Start with the conditions on slide #78. Concentration gradients exists for Potassium, Sodium, and
Chloride, and on both sides of the membrane positive charges balance the negative charges. There is
NO permeability (YET) in the membrane, so the voltage across the membrane is zero…there is no
membrane potential.
2. Now we make the membrane very permeable to Potassium due to the presence of Potassium leak
channels. Potassium ions (+) flow out of the cell along their concentration gradient, until the flow is
balanced by the increasing negativity of the inside of the cell. Net flow of Potassium ions ceases once
the ionic equilibrium potential for Potassium (defined in the glossary) is reached.
3. This is not the whole story of course, otherwise the RMP would be identical to EK. Since we know
that the typical RMP is -70mV and EK is -90mV, something else is at work: Sodium Leak Channels!
Sodium leak channels allow Sodium to flow down it’s electrical and chemical gradients, thus driving
the RMP towards ENa. As discussed below, RMP is much closer to EK than to ENa, even though it is
permeable to both ions.
Remember:
A) The unequal distribution of charges is only at a thin layer on either side of the
membrane…they do not spread to the core of the cell, for example (this would wreak havoc
on delicate protein machinery of the cell). The membrane is thin enough such that the
electrostatic forces between (+) and (-) are felt across the membrane, so the charges stay at
the surface.
B) Small changes in ion concentration = big changes in the membrane potential. So there is
only an infinitesimally small change in the K+ concentration in order to take the membrane
from 0mV to minus 90mV (from 130mM to 129.99999mM). So concentration gradients do
not dissipate under normal conditions.
C) By (brilliantly!) setting up conditions where we have one cation with a high concentration
IN vs OUT (Potassium), and another cation with a high concentration OUT vs IN, by simply
switching the permeability of the membrane to a different ion we can create huge changes in
the voltage across the membrane – this is the essence of graded and action potentials. The
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Resting Membrane Potential
neuron can use this to integrate information from diverse inputs, and communicate rapidly
across long distances.
Activity at what three transmembrane (integral) proteins maintains a resting membrane potential of -70mV?
1) The Sodium / Potassium Pump (AKA the Na+ / K+ ATPase). Responsible for generating the
original concentration gradients for these ions and also maintains them by compensating against the
activity of the leak channels for these ions.
2) Potassium leak channel. Efflux of Potassium across leak channels maintains a voltage across the
membrane that is negative inside with respect to outside.
3) Sodium leak channel. Influx of Sodium (along its electrical and chemical gradient) keeps the
membrane potential slightly more positive than EK (though remember that because there are more
potassium leak channels / more permeability to potassium vs. sodium at rest, RMP is still much
closer to EK than ENa. )
If leak channels for both Na+ and K+ are present, why does the RMP not dissipate over time?
Perpetual activity of the sodium / potassium pump. See above.
Why is the resting membrane potential close to, but slightly more positive than EK? Why is it closer to EK than it is
to ENa?
If potassium was the only ion that the membrane was permeable to at rest, then the RMP would be
equal to EK (recall the definition of ionic equilibrium potential). However, at rest the cell is also
permeable to Na+, so RMP would reflect both EK (-90mV) and ENa (+66mV). However, the resting
membrane is VERY PERMEABLE to potassium and only slightly permeable to sodium…therefore
RMP is close to but slightly more positive than EK.
The equilibrium potential for sodium (Na+) is approximately +66 mV. Identify the net flow of sodium ions (influx,
efflux, or no net movement) if the membrane is permeable only to sodium and the membrane potential is –70 mV?
How about at +66mV? At +90mV?
+66mV is the target value…we want to move the positive charge across the membrane in order to
establish this value. The concentration gradient for Na+ always points in towards the cell (but that
does not matter since it is already built into the calculation of ENa). The electrical gradient will
depend on the voltage in each of the three theoretical circumstance and will dictate the flow:
@ -70mV
Net Influx (strong)
@ +66mV
No Net Movement
@ +90mV
Net Efflux
The equilibrium potential for potassium (K+) is approximately –90mV. Describe the net flow of potassium ions if
the membrane is permeable only to potassium and the membrane potential is –100mV? How about at –90mV? At
+42mV?
Same situation as above, this time trying to move K+ to achieve -90mV.
@ -100mV
Net Influx
@ -90mV
No Net Movement
@ +42mV
Net Efflux (strong)
The equilibrium potential for chloride (Cl-) is approximately –65mV. Describe the net flow of chloride ions if the
membrane is permeable only to chloride and the membrane potential is –80 mV? How about at -65mV? At -30mV?
Be careful, chloride is anionic.
Same situation as above, this time trying to move Cl- to achieve -65mV.
@ -80mV
Net Efflux
@ -65mV
No Net Movement
@ -30mV
Net Influx
Why is it not necessary to know the concentration gradients for Na+, K+, and Cl- in order to answer the previous
three questions?
These are already built into the calculation used (Nernst Equation) to provide us with those values, so
we just need to predict what direction the ion will move based on its charge in order to achieve the
published Eion.
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Resting Membrane Potential
Why do you suppose it is relatively easy for a neuron to restore the resting membrane potential even after it has been
significantly depolarized?
Again, tiny changes in the concentration of an ion = huge changes in the membrane potential.
Consequently there is not a whole lot of ion movement that needs to occur to reestablish resting
conditions. Leak channels, the sodium-potassium pump, and the delayed rectifier current (during
the action potential) all work to restore resting conditions following depolarization.
Hyperkalemia is a condition of excess potassium in the bloodstream and subsequently in the extracellular fluid.
(1)What will happen to the resting membrane potential (and the equilibrium potential for potassium) in
hyperkalemia? (2)Why does hyperkalemia impact other excitable tissues such as cardiac muscle more significantly
than it does the brain? (3)Why do you suppose that hypernatremia (excess sodium in the extracellular fluids) is less
detrimental to nerve function than hyperkalemia?
1) EK would become less negative: since there is a weaker concentration gradient driving K+ , less
efflux would be observed before the concentration gradient is balanced by the electrical gradient.
2) Recall that astrocytes (present in the CNS) actively maintain ionic concentrations in the interstitial
fluid surrounding neurons. No such protective cell exists for other tissues…they are essentially
reliant on the kidneys.
3) The resting membrane potential is heavily dictated by potassium and not by sodium. Test it out in
the bonus activity linked below.
Bonus Activity!!!!!!: Go to www.nernstgoldman.physiology.arizona.edu Click ‘launch now’. Set to ‘Goldman
Equation’ at the upper right corner. Manipulate the permeability as well as the intracellular and extracellular
concentrations of the various ions to observe the effect on the membrane potential and the equilibrium potential for
that ion. You can restore the default settings at the bottom right hand corner.
Practice Questions:
1. Which of the following would you not expect to find in a peripheral nerve fascicle?
A. Motor Nerve Fibers
B. Satellite Cells
C. Schwann Cells
D. Endoneurium
E. All of the above are present
2. Which of the following statements is true?
A. Oligodendrocytes are responsible for myelinating peripheral nerves.
B. Schwann cells can myelinate multiple axons.
C. All axons within the peripheral nervous system are either myelinated or ensheathed.
D. The internode is the gap between two segments of myelin.
E. All of the above are true
3. Which of the following statements is true?
A. Ions can theoretically flow in either direction across an ion channel.
B. At rest the concentration of potassium ions is higher outside of the cell than inside.
C. The resting membrane potential is different in axons than it is in dendrites.
D. In order for sodium ions to depolarize the membrane its concentration gradient must be dramatically
reduced in the process.
E. A and D are both true.
4. The following integral membrane proteins play a critical role in maintaining the resting membrane potential
except:
A. Potassium Leak Channels
B. The Sodium/Potassium ATPase
C. Sodium leak channels
D. Voltage-Gated Sodium Channels
5. All of the following cells are found in the Central Nervous System except:
A. Ependymal Cells
B. Satellite Cells
C. Oligodendrocytes
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Resting Membrane Potential
D. Microglia
6. When the membrane at rest suddenly becomes very permeable to Na+ , you would expect to see __________ of
Na+ ions in order to __________ the membrane.
A. Net efflux, Hyperpolarize.
B. No net movement, Have no effect upon
C. Net influx, Depolarize
D. Net efflux, Depolarize
7. The gaps between myelin segments along myelinated axons in the PNS are called:
A. Internodes
B. Mesaxons
C. Ganglia
D. Nodes of Ranvier
8. If you decreased the extracellular concentration of potassium, what would happen to the resting membrane
potential?
A. It would be more positive
B. It would be more negative
C. It would be unaffected
D. There is not enough information
(Opposite situation of hyperkalemia)
9. If a cell at resting membrane potential increased its permeability to sodium, what would happen to the ionic
equilibrium potential for sodium?
A. It would be more positive
B. It would be more negative
C. It would be unaffected
D. There is not enough information
(Recall the calculation of an ionic equilibrium potential…nowhere does it involve calculating for
permeability. ENa would be the same value regardless if many channels or not channels are actually open to
Na+. ENa would only change if you manipulated the external or internal concentration of sodium ions.)
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