1.

A patch of membrane at 37C has the following intra- and extra-cellular ionic concentrations and
resting conductances:
Ion [C]
in
(mM) [C]
out
(mM) g
i
(mS/cm
2
)
K
+
140 5 0.07
Na
+
15 145 0.02
If a synapse in this patch of membrane has the reversal potential , determine
whether the synapse is excitatory or inhibitory.
syn
65 mV E =
2. Consider an action potential with a waveform that can be approximated by a triangle, as given in
the figure below. Assume that the tail of the action potential spatial waveform is at position 0 x = ,
that no currents are being injected into the intra- or extra-cellular space from external sources, and
the intra- and extra-cellular resistances per unit length are 1.25 M cm
i
r = and 12.5 k
e
= cm r ,
respectively. If this action potential is propagating (without dissipation) along an unmyelinated
axon in the x + direction with velocity 6 m/s, calculate the resulting local circuit currents, i.e., the
transmembrane currents and the axial intra- and extra-cellular currents as a function of position x .
0 0.5 1 1.5 2
0
10
20
30
40
50
60
70
80
90
100
Time (ms)
V

(
m
V
)

3. A known solution to the Hodkin-Huxley (nonlinear) cable equation is ( ) ( ut x V t x V = , ) , that is, a
stable action potential waveform that travels along an unmyelinated axon with constant
propagation velocity . Derive the dependency of u on the diameter of the axon d. u
4. A linear cable of electrotonic length 2 terminates in a killed end. What is the ratio of this cables
input resistance to the input resistance of semi-infinite cable with the same diameter and internal
and membrane resistivities? What is the ratio of the membrane potential at the midpoint of the
cable to the membrane potential at the start of the cable?


5. A Calcium channel in a cell membrane obeys the assumptions of the constant field (GHK) model.
a) Show how the Nernst Equation can be derived from the GHK Current Equation:
[ ] [ ]

1 e
C e C
.) (
in out 2
RT zFV
RT zFV
FV z const I
b) Find the Calcium equilibrium (reversal) potential in units of millivolts for the cell membrane at
20C when [Ca
2+
]
in
= 10
-4
mM and [Ca
2+
]
out
= 2.1 mM.
c) Plot the approximate I-V relationship. Is this channel inwards rectifying or outwards rectifying?
6. Consider a spherical cell with diameter d 10 m = and the parallel-conductance model for a
membrane patch shown below.
g
Na
= 0.12
mS/cm
2
g
K
= 0.18
mS/cm
2
C
m
= 1.0
F/cm
2
inside
outside
E
Na
=
+59 mV
E
K
=
101 mV

Find both:
a) the resting transmembrane potential , and
rest
V
b) the membrane time constant .


7. The results of a voltage-clamp experiment are shown below.
0 100 200
60
40
20
0
Time (ms)
V

(
m
V
)
0 100 200
40
20
0
20
40
Time (ms)
I

(
n
A
)
80 60 40
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
V (mV)
y

27 nA
13 nA

Assume that the measured transmembrane current ( , ) I V t is comprised of a passive leakage current
( ( ) )
L L L
I V g V E = and a time- and voltage-dependent current
(
( , )
y y
)
y
I V t g y V E = , where the
dynamics of the gating particle are first-order, i.e., y d ( , ) d ( )
y
y V t t y y

= . The time-constant
y
is independent of voltage, whereas the voltage dependence of the steady-state value ( ) y V

is
shown in the figure above. It is known that the Nernst equilibrium potential . 50 mV
y
E = +
From the results of the voltage-clamp experiment, find the values of , and
L
g
L
E
y
g .
8. Consider an action potential that is approximated by the rectangular spatial waveform shown below.

The fiber has a radius of and an axoplasm conductivity of 4 m a = 0.02 S/cm
i
= .
Find the strength and location of the equivalent (lumped) sources.


9. Consider a chloride ion channel in a cell with an intracellular chloride concentration of
[ ] Cl 40 mM
i
= and an extracellular concentration of [ ] Cl 556 mM
e
= . The cell is at a temperature
of 0C
a) Find the Nernst equilibrium potential for chloride.
b) If the transmembrane potential of the cell is presently at 70 mV
m
V = , is there a net efflux of
chloride ions through this channel or a net influx?
10. Consider a spherical cell with diameter 10 m d = and the parallel-conductance model for a
membrane patch shown below.
g
Na
= 0.1
mS/cm
2
g
K
= 0.8
mS/cm
2
C
m
= 0.7
F/cm
2
inside
outside
E
Na
=
+55 mV
E
K
=
90 mV

Find the steady-state transmembrane potential for the following two cases:
a) when no current is being injected into the cell, and
b) when a current is injected into the intracellular space.
inj
15.7 pA I =
11. Show that the alternative formulation of the Hodgkin-Huxley potassium gating particle dynamics:
( ) d d
n
n t n n

= , where ( )
n n n
n

= + and ( ) 1
n n n
= + ,
is identical to the standard formulation ( ) d d 1
n n
n t n n = .
12. You have two unmyelinated axons, identical except that axon #2 has an axoplasmic resistivity that
is double that of axon #1. Assuming that the axons can be approximated by infinite cables and that
: 0
e
r
a) What are the relative conduction velocities of the two cables?
b) What are the relative input resistances of the two cables?
c) What are the relative space constants of the two cables?
d) What are the relative time constants of the two cables?


13. Consider an action potential with the spatial waveform illustrated in the figure below.
0 0.5 1 1.5
0
30
60
90
x (cm)
v
m

(
m
V
)

The relative transmembrane potential can be described by:
2
0, for 0,
2
402.15 e sin , for 0 1.5,
0, for 1.5,
m
x c
x
v x
d
x

<

>

x
where x is in units of cm, and 0.4135 cm c = 3 cm d = .
Assume that no currents are being injected into the intra- or extra-cellular space from external
sources and the intra- and extra-cellular resistances per unit length are 1.25 M cm
i
r = and
12.5 k cm
e
r = , respectively.
Calculate the local circuit currents, i.e., the transmembrane currents and the axial intra- and extra-
cellular currents as a function of position x .
14. You have two unmyelinated axons, identical except that their diameters are 5 m and 10 m.
Assuming that the axons can be approximated by infinite cables:
a) What are the relative conduction velocities of the two cables?
b) What are the relative input resistances of the two cables?
c) What are the relative space constants of the two cables?
d) What are the relative time constants of the two cables? (20 pts)


15. An action potential with an approximately triangular spatial waveform is propagating along a fiber
in the x + direction, as shown below.
0 6 12 18
0
20
40
60
80
100
x (cm)
v
m

(
m
V
)
propagation direction

The fiber has a radius of and an axoplasmic conductivity of 3m a = 0.03S/cm
i
= .
a) Find the dipole source densities for the regions 0 x = to 12 cm and to 18 cm. 12 x =
b) Find the strength(s) and location(s) of the lumped monopole source(s).
16. An excitable cell has the following intra- and extra-cellular ionic concentrations:
Ion [C]
in
(mM) [C]
out
(mM)
K
+
400 20
Na
+
50 440
Assume the cell membrane obeys the parallel-conductance model with just sodium and potassium
channels present.
a) If the temperature is 24C, what are the potassium and sodium Nernst equilibrium potentials,
and , respectively?
K
E E
Na
b) If the resting potassium and sodium conductances are
2
K
0.8 mS cm g = and
2
Na
0.2 mS cm g = , respectively, then what is the resting transmembrane potential of the cell,
?
rest
V
c) When the membrane is at rest, i.e.,
rest m
V V = , what are the potassium and sodium current
densities,
K
I and
Na
I , respectively?
For each of these ion species, state whether the calculated current corresponds to an influx or
efflux of ions.
d) If a constant current of
2
inj
5 A cm I = is injected into the intracellular space, what is the
steady-state transmembrane potential ?
m
V


17. Transmembrane currents measured in a squid axon from a voltage-clamp experiment are shown
below.

The membrane was initially held at voltage 60 mV
h
V = and was stepped at time to voltage
shown to the right of each current trace.
0 t =
c
V
The results can be interpreted by considering a parallel-conductance model with voltage-gated
sodium and potassium channels and a passive leakage channel.
a) What caused the small sustained inward current when the membrane was stepped to
? 125 mV
c
V =
b) Why did the peak amplitude of the early inward current ( at 1 ms t ) increase when was
increased from to ?
c
V
30 mV ~ 0 mV
c) Why did the peak amplitude of the early inward current decrease when was increased from
to ?
c
V
~ 0 mV 40 mV +
d) What is the approximate threshold potential of this axon?
thr
V
e) If the early inward current is carried by sodium, what is the approximate sodium equilibrium
potential for this axon?
Na
E
f) If the late outward current is carried by potassium and
K
65 mV E for this axon, why is there
no reversal of the late outward current in any of these measurements?


18. The conductance waveform for a postsynaptic current (PSC) can be approximated by an alpha
function:
( )
peak
syn
const e
t t
g t t

= .
Prove that:
a) the conductance reaches its maximum value of ( )
syn peak
g t g = at time
peak
t t = , and
b) the constant must be equal to
1
peak peak
e g t .
19. The subthreshold behaviour of a postsynaptic membrane patch can be described by the circuit
diagram shown below.
g
syn
(t)
R =
90 M
C =
90 pF
inside
outside
E
syn
=
+20 mV
V
rest
=
65 mV

a) Is this synapse excitatory or inhibitory? Briefly explain why.
b) If the synaptic reversal potential were equal to 20 mV, would the synapse be excitatory
or inhibitory? Briefly explain why.
syn
E
c) Calculate the membrane time constant when there is no synaptic input, i.e., ( )
syn
0 g t = .
d) Calculate the membrane time constant when the synaptic input is at its maximum, i.e.,
. ( )
syn peak
10 nS g t g = =


20. An excitable cell has the following intra- and extra-cellular ionic concentrations:
Ion [C]
in
(mM) [C]
out
(mM)
K
+
150 15
Na
+
10 130
Assume the cell membrane obeys the parallel-conductance model with a leakage channel in
addition to sodium and potassium channels, with resting potassium, sodium and leakage
conductances of
2
K
1.0 mS cm g = ,
2
Na
0.05 mS cm g = and
2
leak
0.3 mS cm g = , respectively.
a) If the temperature is 40C, what are the potassium and sodium Nernst equilibrium potentials,
and , respectively?
K
E E
Na
b) If the resting transmembrane potential is
rest
54 mV V = , then what is the Nernst equilibrium
potential of the leakage channel ?
leak
E
c) When the membrane is at rest, i.e.,
rest m
V V = , what are the potassium, sodium, and leakage
current densities,
K
I ,
Na
I and
leak
I , respectively?
For each of these ion species, state whether the calculated current corresponds to an influx or
efflux of ions.
d) If a constant current of
2
inj
4 A cm I = is injected into the intracellular space, what is the
steady-state transmembrane potential ?
m
V


21. Consider the neuron shown below.
Soma
Dendrites
Excitatory
synapse
x

Assume:
1. the dendrite with the excitatory synapse can be modeled by an infinite uniform cable with a
radius of and an intracellular resistivity of 1m a = 187 cm
i
R = ;
2. the extracellular axial resistance is negligible, i.e., 0
e
r ;
3. the membrane specific resistance is and the membrane specific
capacitance is
2
10 k cm
m
R =
2
1F cm
m
C = ;
4. the threshold potential at the soma is 25 mV above the resting membrane potential; and
5. synaptic input can be approximated by a step current injection that causes a steady-state
depolarization of at the site of the synapse. 30 mV
m
v =
a. If the synaptic input stays on long enough for the membrane potential at the soma to reach its
steady state, how close does the synapse need to be to the soma (i.e., what is the minimum
distance x ) in order for an action potential to be generated?
b. If the synapse is 40 from the soma, how long does it take for an action potential to be
generated after the onset of the synaptic input? Is this time greater than or less than the
membrane time constant? (30 pts)
m


22. An action potential with the spatial waveform illustrated below is propagating along a fiber.
0 2 4 6 8 10 12
0
10
20
30
40
50
60
70
80
x (cm)
v
m

(
m
V
)

The relative transmembrane potential can be described by:
peak
2
2
138.55 e , for 0,
0, for 0,
x x
m
x x
v
x

=

<

where x is in units of cm and
peak
2 cm x = .
The fiber has a radius of and an axoplasmic conductivity of 6 m a = 0.02 S/cm
i
= .
a) Find expressions describing two dipole source density regions generated by the action potential.
b) Find expressions describing three monopole source density regions generated by the action
potential.
c) Find the strengths of two lumped dipole sources based on the dipole source densities from part
a. above.
d) Find the strengths of three lumped monopole sources based on the monopole source densities
from part b. above.


23. The subthreshold behaviour of neural soma can be described by the circuit diagram shown below.
R =
80 M
C =
70 pF
inside
outside
V
rest
=
60 mV
g
I
(t)
E
I
=
80 mV
g
E
(t)
E
E
=
+20 mV

The neuron has a threshold potential of
th
40 mV V = . Synaptic input onto this soma consists of
one excitatory synapse and one inhibitory synapse, which produce the currents:
( )[ ] ( )[ ]
E E E I I I
and ,
m m
I g t V E I g t V E = =
respectively.
Consider the case where the membrane is at rest (i.e.,
rest m
V V = ) and an excitatory synaptic input
causes the excitatory conductance to step instantaneously from
E
0 nS g = to .
E
20 nS g =
a) If there is no inhibitory synaptic input, how long after the onset of the excitatory input does the
membrane potential reach the threshold potential ? Is this time shorter or longer than
the resting membrane time constant?
m
V
th
V
b) If an inhibitory synaptic input arrives at the same time as the excitatory input and causes an
instantaneous step in the inhibitory conductance , how large does need to be to prevent
the membrane potential from ever reaching the threshold potential ?
I
g
I
g
m
V
th
V