1

Researchers are studying how the membrane potential of a postsynaptic neuron changes in
response to neurotransmitter stimulation. Baseline measurements determine that the resting
membrane potential is generated by high membrane permeability for a particular ion. When
neurotransmitter stimulation begins, ligand-gated ion channels open (black arrow) and increase
the membrane permeability for a different ion, causing a change in membrane potential. This
triggers the delayed opening of voltage-gated ion channels (red arrow), which increase the
membrane permeability for a third type of ion. The results of the experiment are shown in the
graph below.

The equilibrium potentials of different ions under physiologic conditions are as follows:

ENa = +60 mV
EK = −90 mV
ECl = −75 mV
ECa = +125 mV
Which of the following options would best explain the changes in this neuron's membrane
potential during the experiment?

Physiology 1 Page 1
Equilibrium potentials of cellular ions reflect how they affect the membrane potential if the
membrane were permeable solely for that ion. The resting membrane potential shown in the
graph is negative, indicating that at rest, the membrane is permeable to an ion with a negative
equilibrium potential (potassium or chloride). Opening of ligand-gated ion channels in
response to neurotransmitter binding (black arrow) causes an increase in membrane potential
to above zero. This indicates that the membrane has become permeable for an ion with
a positive equilibrium potential (sodium or calcium). Opening of voltage-gated ion channels in
response to the change in membrane potential (red arrow) causes a drop in membrane
potential, indicating that the membrane becomes permeable to an ion with a negative
equilibrium potential (potassium or chloride).
(Choices A and B) If the membrane were permeable for sodium at rest, the resting membrane
potential would be positive as the equilibrium potential of sodium is +60 mV.
(Choices C and D) Had the membrane become more permeable for calcium or sodium
following the opening of the voltage-gated ion channels, the membrane potential would have
remained positive as both ions have positive equilibrium potentials.
Educational objective:
Changes in membrane potential occur in response to changes in neuronal membrane
permeability to various cellular ions. The more permeable the membrane becomes for a
cellular ion, the more that ion's equilibrium potential contributes to the total membrane
potential.

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2

Molecular biologists perform a series of experiments to characterize the electrophysiologic

properties of human muscle cells. The resting membrane potential for an isolated muscle cell is
determined to be -70 mV. The equilibrium potentials for important ions under normal
physiologic conditions are as follows:
ENa = + 60 mV
EK = - 90 mV
ECl = - 75 mV
ECa = + 125 mV
EMg = 0 mV
If physiologic conditions are maintained, which of the following ions would most likely flow out
of the cell after opening of their respective ion channels?

Magnesium and calcium [1%]

A.

Magnesium and chloride [1%]

B.

Potassium and chloride [42%]

C.

Potassium only [42%]

D.

Sodium and calcium [12%]

E.

Physiology 1 Page 3
Na+, K+, and Cl- are the main ions that determine the electrical potential difference (voltage)
across a membrane (membrane potential). Under normal physiologic conditions, there is a low
concentration of Na+ and Cl- in the cell and high concentration of K+ in the
cytoplasm. Conversely, the extracellular space has a high concentration of Na+ and Cl- ions and
low concentration of K+ions.
Because intracellular K+ concentration is much greater than its extracellular concentration,
opening of cellular potassium channels leads to K+ efflux from the cell along the
K+ concentration gradient. Within the cell, the positive charge of the K+ ions is normally
neutralized by the negative charge of intracellular anions (eg, phosphates and proteins) that are
trapped in the cell. As K+ ions leave the cell, negatively charged anions accumulate along the
inner side of the cell membrane. This continually increasing negative charge attracts the
positively charged K+ ions back into the cell. When the difference in concentration (diffusion
potential) of K+ inside and outside the cell is large, the efflux of K+ ions will continue despite the
increasing negative charge. At a certain point, however, the negative intracellular charge
(electrical potential) of the membrane becomes large enough that the number of K + ions it
attracts into the cell equals the number of K+ ions that leave the cell along the concentration

Physiology 1 Page 4
attracts into the cell equals the number of K+ ions that leave the cell along the concentration
gradient. The electrical potential difference that moves K+ ions into the cell at the same rate as
they leave the cell along the concentration gradient is called the equilibrium potential.
Educational objective:
When a specific ion channel opens, the respective ions will flow across the membrane in a
direction that brings the resting membrane potential closer to that ion's equilibrium potential.

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3

The resting membrane potential for an isolated muscle cell is -70 mV. Equilibrium potentials for
important ions are given below:
ENa = + 60 mV
EK = - 80 mV
ECl = - 70 mV
ECa = + 125 mV

Which of the following most likely forms the resting membrane potential of the cell?

High potassium conductance and some sodium conductance [54%]

A.

High chloride conductance and some sodium conductance [4%]

B.

High calcium conductance and some chloride conductance [3%]

C.

High potassium conductance and some chloride conductance [14%]

D.

High potassium conductance only [22%]

E.

The resting potential refers to the difference in charge across the cell membrane at rest (when
there is no signaling activity). The membrane prevents the free diffusion of ions, and generally
there is an excess of positive ions outside the cell and an excess of negative ions in the
cytoplasm. This separation of positive and negative charges across the cell membrane gives rise
to an electrical potential difference that ranges from -60 to -80 mV; the typical resting
membrane potential of a cell is -70 mV.
The cytoplasm of a typical cell is characterized by a low concentration of Na and high
concentration of K. The extracellular fluid is inversely rich in Na and low in K. This difference in
Na and K concentration is maintained by the Na,K-ATPase, which pumps three Na ions out of
the cell for every 2 K ions allowed into the cell.
Every charged ion that the cell membrane is permeable attempts to push the resting
membrane potential of the cell toward its equilibrium potential. The resting membrane
potential can therefore be viewed as a combination of the equilibrium potentials of the ions
that can penetrate the cell membrane. Each permeable ion does not contribute equally to the
membrane potential; it is obvious that the resting membrane potential does not equal the
average of the different equilibrium potentials. The greater the permeability of a given ion, the
greater its contribution to the resting membrane potential will be. Ions with little permeability
will contribute very little to the resting membrane potential. In the resting cell the permeability

Physiology 1 Page 6
will contribute very little to the resting membrane potential. In the resting cell the permeability
of the membrane for K is much higher than that for Na. Outflow of K ions through non-gated
channels maintains the negative charge inside the membrane, which approaches the
equilibrium potential for K. There are, however, a small number of channels that allow the flow
of Na into the cell. This small influx of Na ions decreases the membrane potential, and for this
reason the resting potential of the membrane is always less negative than the equilibrium
potential for K (Choice A).
(Choice B) If the chloride equilibrium potential is -70 mV and the resting membrane potential
is -70 mV, then chloride would need to be the only membrane permeable ion with no
contribution from other ions. Chloride, in reality, plays little role in the determination of the
membrane potential.
(Choice C) High calcium conductance would make the resting membrane potential positive, and
the question stem states that the membrane potential is -70 mV.
(Choice D) High potassium conductance does occur at rest and is the largest contributor to the
resting membrane potential. Chloride plays little to no role in the determination of the resting
membrane potential.
(Choice E) If a high potassium conductance were the only contributor to the resting membrane
potential, then the membrane potential would be the same as the potassium equilibrium
potential.
Educational Objective:
The resting membrane potential is the difference in the electrical charges across the cell
membrane under steady-state conditions. The ions that are most permeable to the cell
membrane make the largest contribution to the resting membrane potential. In general, a high
potassium efflux and some sodium influx are responsible for the value of the resting potential,
which is typically about -70 mV.

Physiology 1 Page 7
4

A researcher is investigating a new antiseizure drug that binds to and activates GABA-A
receptors in the central nervous system. During the experiment, she isolates a nerve and uses a
microelectrode to measure its membrane potential under physiologic conditions. The resting
potential of the nerve is found to be −70 mV. Which of the following membrane potentials will
most likely be recorded from this neuron following exposure to the new drug?

−75 mV [74%]

A.

−70 mV [8%]
B.

−55 mV [6%]
C.

0 mV [2%]
D.

+25 mV [1%]
E.

+40 mV [1%]
F.

+60 mV [3%]
G.

+125 mV [1%]
H.

Physiology 1 Page 8
The GABA-A receptor is an ionotropic receptor (eg, part of an ion channel) that regulates the
flow of negatively charged chloride ions across the neuronal cell membrane. A drug that binds
to and activates GABA-A receptors will increase the conductance of chloride ions, causing
passive transport down the concentration gradient into the cell interior. This causes the
membrane potential to become hyperpolarized (more negative than the resting membrane
potential) by approaching or reaching the equilibrium potential for chloride (−75 mV). A cell
that becomes hyperpolarized is temporarily made refractory to firing an action potential.
(Choice B) Exposure to the experimental drug will make the neuronal membrane potential
more negative than the resting membrane potential due to the opening of chloride channels.
(Choice C) The opening of ligand-gated (controlled by binding of neurotransmitters) sodium
channels allows for the initial influx of positively charged sodium ions. This causes a graded
depolarization of the neuronal cell membrane toward the threshold for firing an action
potential (−55 mV).
(Choices D, E, F, and G) Once the threshold membrane potential is reached, fast voltage-gated
sodium channels open to mediate the upstroke phase of the neuronal action potential. During
this time, the membrane potential becomes even more positive due to the rapid influx of
sodium ions and causes the membrane potential to approach the equilibrium potential for
sodium (+60 mV).
(Choice H) The influx of positively charged calcium ions can raise the membrane potential even
further (more positive than +60 mV) toward the equilibrium potential for calcium ions (+125
mV).
Educational objective:
A drug that binds to and activates GABA-A receptors (or enhances their activity) will increase
the conductance of chloride ions, leading to increased passive transport of chloride into the cell
interior. This causes the membrane potential to become hyperpolarized (more negative than

Physiology 1 Page 9
interior. This causes the membrane potential to become hyperpolarized (more negative than
the resting membrane potential) by approaching or reaching the equilibrium potential for
chloride.

Physiology 1 Page 10
5

Two graphs illustrating the transport of low molecular weight solutes across the plasma
membrane are shown on the slide below.

Which of the following best explains the difference in the shape of the curves?

Concentration difference across the membrane [10%]

A.

Diffusion area [4%]

B.

Membrane thickness [2%]

C.

Oil/water partition coefficient [5%]

D.

Protein carrier [77%]

E.

The image above illustrates the difference between the rate of transport of solute across the
cell membrane in simple diffusion (line 2) and carrier-mediated transport (line 1). The
difference in the shape of the graphs is explained by the presence of a carrier protein in the
scenario represented by line 1.
There are two types of diffusion:
1. Simple diffusion – molecules move through a membrane without the help of carrier
proteins.
2. Facilitated diffusion – requires carrier proteins.
Carrier proteins are typically transmembrane proteins that possess binding sites for the
substrate they transport. They bind extracellular ions and molecules forming a carrier-
substrate complex. Binding is followed by movement of the complex across the cell membrane
to the intracellular space, where the substrate is released into the cytoplasm. Because there is
a finite number of carrier proteins in the cell membrane, and these carrier proteins require a
discrete amount of time to pass a single molecule or ion through the membrane, saturation is

Physiology 1 Page 11
discrete amount of time to pass a single molecule or ion through the membrane, saturation is
an important property of carrier-mediated diffusion (facilitated diffusion). Once all of the
carrier molecules are bound by substrate, no further diffusion can occur until a carrier protein is
vacated. This maximum rate of transport is referred to as the transport maximum (Tm) and is
similar in principle to the Vmax in standard enzyme kinetics.
(Choices A – D) The other factors mentioned are not significantly different between simple
diffusion and facilitated diffusion.

The difference in the concentration of the substrate across the membrane is called
concentration gradient (ΔP). The higher the concentration gradient the higher the rate of
transport of the molecule or ion across the membrane.
The larger the surface area (SA) the greater the rate of diffusion. If the thickness of the
membrane (T) is higher (eg, lung fibrosis) then the rate of diffusion would be slower. High
molecular weight (MW) compounds diffuse slowly.
A high oil-water partition coefficient means that a solute is much more soluble in oil than in
water. This characteristic is widely used to describe the pharmacokinetic properties of general
anesthetics.
Educational Objective:
Carrier-mediated transport includes facilitated diffusion and active transport. Movement of
substrate across the cell membrane by these mechanisms depends on the presence of carrier
proteins in the membrane. Transport mechanisms utilizing proteins are able to be saturated.

Physiology 1 Page 12
6

A 34-year-old man comes to the emergency department complaining of weakness, dizziness,

and paresthesias involving his face and extremities. He has never had symptoms like this
before. Two hours earlier, he ate fish at a new Japanese restaurant. Neurological examination
shows reduced muscle strength and decreased deep-tendon reflexes. Which of the following
parts of the action potential curve is most likely impaired in this patient?

A [7%]
A.

B [74%]

B.

C [5%]
C.

D [8%]
D.

E [4%]
E.

Physiology 1 Page 13
This patient’s constellation of symptoms (ie, paresthesias, weakness, dizziness, nausea) and
history of fish consumption are strongly suggestive of food poisoning by pufferfish, a Japanese
delicacy. Pufferfish can be lethal if not properly prepared. It is necessary to remove the organs
containing high quantities of tetrodotoxin, a toxin produced by microorganisms associated with
the fish.
Tetrodotoxin binds to voltage-gated sodium channels in nerve and cardiac tissue, preventing
sodium influx and depolarization. Symptoms of tetrodotoxin poisoning occur quickly after
ingestion and include dizziness, weakness, loss of reflexes, paresthesias of the face and
extremities, nausea, vomiting, and diarrhea. Higher exposures can cause severe hypotension
and general paralysis; death can occur from respiratory failure and hypotension. Treatment
includes supportive care and intestinal decontamination with gut lavage and charcoal.
(Choice A) The resting potential is equal to approximately -70 mV. It is maintained by high
membrane K+permeability and low Na+permeability. K+ efflux occurs via non-gated K+ channels
(leak channels).
(Choice C) Overshoot represents the maximal value of the action potential during which the
membrane potential is positive. At this point, open sodium channels become inactivated and
close, preventing further increase in the membrane potential.
(Choice D) Repolarization results from closure of Na+ channels and simultaneous opening of
K+ channels. This results in a sharp decrease in Na+ conductance and a significant increase in
K+ conductance. Potassium efflux is responsible for returning the membrane potential to the
resting potential.
(Choice E) Hyperpolarization occurs for a short moment following repolarization due to the
slow closure of voltage-gated potassium channels. The membrane potential becomes more
negative than the normal resting potential and approaches the K+ equilibrium potential of -85
mV. When the voltage-gated K+ channels close, the membrane potential returns to the resting
value.
Educational objective:
Pufferfish poisoning is caused by tetrodotoxin, a neurotoxin produced by microorganisms
associated with the fish. Tetrodotoxin binds to voltage-gated sodium channels in nerve and
cardiac tissue, preventing sodium influx and depolarization.

Physiology 1 Page 14
7

Neurophysiologists are studying recordings of the membrane potential from a giant squid axon.
A portion of their recordings is shown on the slide below.

The membrane is most permeable to potassium ions at which of the following points?

A [2%]
A.

B [2%]
B.

C [17%]
C.

D [67%]

D.

E [8%]
E.

Physiology 1 Page 15
The graph depicts the potential voltage changes across a cell membrane; these changes
(depolarization, repolarization, hyperpolarization, and resting potential) are collectively known
as the action potential. The action potential occurs due to changes in the membrane
permeability to Na+ and K+ ions. The membrane potential of an excitable cell (eg, nerve and
muscle) cycles through the following stages:
Exhibit Display

1. Resting potential (Choice A): Usually equal to -70 mV. It is maintained by high resting

Physiology 1 Page 16
 1. Resting potential (Choice A): Usually equal to -70 mV. It is maintained by high resting
membrane permeability to K+and low permeability to Na+. K+ efflux occurs via non-gated
K+ channels (leak channels). While at the resting potential, the inner side of the
membrane is negatively charged with respect to the outer surface of the membrane.
2. Depolarization: Occurs due to opening of voltage-gated Na+ channels with rapid influx of
Na+ into the cell. The large influx of Na+ leads to an increased positive charge inside the
membrane known as depolarization (Choice B). Overshoot refers to the maximal value of
the action potential during which the membrane potential obtains a positive value
(approximately +35 mV) (Choice C).
3. Repolarization (Choice D): Results from closure of Na+ channels and simultaneous
opening of K+ channels. This causes a sharp decrease in the membrane permeability to
Na+ and a significant increase in K+ permeance that exceeds that of the resting
membrane. K+ efflux is responsible for returning the membrane potential back to the
resting potential.
4. Hyperpolarization (Choice E): Occurs because the voltage-gated K+ channels remain open
for a short time after repolarization is completed. The membrane potential thus becomes
more negative than the normal resting potential and approaches the K + equilibrium
potential of -85 mV. When the voltage-gated K+ channels close, the membrane potential
returns to the resting value maintained by the non-gated K+ channels.

Educational objective:
The action potential results from changes in the membrane permeability to K + and
Na+ ions. Depolarization results from massive influx of Na+ through voltage-gated
Na+ channels. Repolarization occurs due to closure of voltage-gated Na+channels and opening
of voltage-gated K+ channels. K+ ion permeance is highest during the repolarization phase of
the action potential.

Physiology 1 Page 17