ECE795 Math Practice Solns PDF

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 =
The synapse type depends on the value of
syn
E relative to , the resting
transmembrane potential.
rest
V
First, the Nernst equilibrium potentials for sodium and potassium must be calculated.
The temperature 37C corresponds to an absolute temperature of
, and potassium and sodium both have valences of Z = +1.
Given the ionic concentrations from the table above, the sodium and potassium
Nernst equilibrium potentials are:
273 37 310 K T = + =

[ ]
[ ]
Na
Na
Na Na
8.314 310 15
ln ln 60.6 mV
1 96487 145
i
e
C
RT
E
Z F C

= = = +

,
and
[ ]
[ ]
K
K
K K
8.314 310 140
ln ln 89.0 mV
1 96487 5
i
e
C
RT
E
Z F C

= = =

,
respectively.
From the parallel-conductance model, the resting potential is then:
( ) ( )
Na Na K K
rest
Na K
0.02 60.6 mV 0.07 89.0 mV
55.8 mV
0.02 0.07
g E g E
V
g g
+ +
= = =
+ +
.
Thus,
syn rest
E V < and consequently this synapse is inhibitory.
Dr. Ian C. Bruce November 17, 2007 Page 1 of 40
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 cm
e
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
)

From the information that the action potential is propagating without dissipation at a
constant velocity of 6 m/s (= 0.6 cm/ms), we know that:
i. The axon is active (nonlinear), so we can only use the cable equations that apply
to nonlinear membranes; and
ii. The spatial action potential waveform must be of the form:
( ) ( , 0 V x t V x t = ) .6 ,
where x is the position along the axon in units of cm and t is the time in units of
ms.
For the temporal action potential waveform shown above, the spatial extent will be
1.2 cm, and for propagation in the x + direction, the spatial action potential waveform
will be pointing in the opposite direction, as shown in the top panel of the figure
below.
0 0.3 0.6 0.9 1.2
0
30
60
90
V

(
m
V
)
0 0.3 0.6 0.9 1.2
300
200
100
0
100
V
/
x

(
m
V
/
c
m
)
0 0.3 0.6 0.9 1.2
400
200
0
200
x (cm)
2
V
/
x
2

(
m
V
/
c
m
2
)

To determine the transmembrane currents resulting from the spatial waveform shown
above, we make use of the cable equation for the transmembrane currents:
2
2
1
m
i e
V
I
r r x
=
+
,
which is valid for both linear and nonlinear cables.
The first and second spatial derivates of the action potential waveform are shown in
the middle and bottom panels, respectively, of the figure above. The delta Dirac
functions at x = 0, 0.9 and 1.2 cm have areas of 100, 400 and 300 mV/cm,
respectively.
Dividing by the sum of the intra- and extra-cellular resistances per unit length gives
the transmembrane currents
m
I shown in the top panel of the figure below. The delta
Dirac functions at x = 0, 0.9 and 1.2 cm have areas of 0.0792, 0.3168 and 0.2376
A, respectively.
To obtain the intra- and extra-cellular axial currents
i
I and
e
I , respectively, we make
use of the cable equations:
;
i e
m m
I I
I I
x x

= =

,
which are valid for both linear and nonlinear cables. Integrating the solution for
m
I
from 0 to x gives the solutions for
i
I and
e
I shown in the middle and bottom panels,
respectively, of the figure below. The magnitudes of the axial currents are 0.0792 A
between 0 and 0.9 cm and 0.2376 A between 0.9 and 1.2cm.
We note that the solutions for
m
I ,
i
I and
e
I together satisfy Kirchoffs current law.
0 0.3 0.6 0.9 1.2
0.5
0
0.5
I
m

(
A
/
c
m
)
0 0.2 0.4 0.6 0.8 1 1.2
0.5
0
0.5
I
i

(
A
)
0 0.2 0.4 0.6 0.8 1 1.2
0.5
0
0.5
x (cm)
I
e

(
A
)

3. A known solution to the Hodgkin-Huxley (nonlinear) cable equation is
( ) x ut , that is, a stable action potential waveform that travels along
an unmyelinated axon with constant propagation velocity u . Derive the
dependency of u on the diameter of the axon d .
( ) , V x t V =
The derivation is given on slides 6569 of Lecture #3 with u , the propagation
velocity.
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?
For a linear finite cable of electronic length 2 L = terminating in a killed end, the
ratio of this cables input resistance to the input resistance of a semi-infinite cable is:
( ) ( )
in
tanh tanh 2 0.964.
R
L
R
= = =
The ratio of the membrane potential at the midpoint of the cable to the membrane
potential at the start of the cable is:
( ) ( )
( )
( )
( )
0
1 sinh sinh 2 1
0.324.
sinh sinh 2
V X L X
V L
=
= = =
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?
a. Nernst equilibrium is achieved when 0 I = . Solving the GHK Current Equation
for V when 0 I = gives:
[ ] [ ]
[ ] [ ]
[ ] [ ]
[ ]
[ ]
2 out in
out in
out in
in
out
C e C
( .)
e 1
C e C 0
C e C
C
e
C
zFV RT
zFV RT
zFV RT
zFV RT
zFV RT
I const z FV

= =

=
=
=
0

[ ]
[ ]
[ ]
[ ]
in
out
in
out
C
log
C
C
log ,
C
e
e
zFV RT
RT
V
zF

=

=

which is the Nernst equation.
b. The calcium equilibrium potential
Ca
E for these parameters is:
[ ]
[ ]
( )
4
in
Ca
out
Ca 8.314 273 20
10
log log 125.2 mV.
Ca 2 96487 2.1
e e
RT
E
zF

+
= = =

+

c. The calcium current
Ca
I has the form illustrated in the figure below. Because this
channel passes larger inwards (ve) currents than outwards (+ve) currents, it is
inwards rectifying.
100 50 0 50 100 150 200
0.2
0.15
0.1
0.05
0
V
m
(mV)
I
C
a

(
a
.
u
.
)

6. Consider a spherical cell with diameter 10 m d = 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:
d. the resting transmembrane potential
rest
V , and
e. the membrane time constant .
a. The transmembrane potential is:
( ) ( )
Na Na K K
rest
Na K
0.12 59 mV 0.18 101mV
37.0 mV
0.12 0.18
g E g E
V
g g
+ +
= = =
+ +
.
Note that the transmembrane potential is independent of the cell surface area
2
4 A r = ( ) 4 5 m 3.142 10 cm = =
2
6 2
. The conductances per unit area could
be multiplied by A to obtain the absolute conductances for the whole cell, but A
would cancel out in the numerator and denominator of the equation for V .
rest
b. The membrane time constant is:
6
3 3
Na K
1 10
3.3 ms
0.12 10 0.18 10
C C
RC
G g g
= = = = =
+ +
.
Note that the membrane time constant is also independent of the cell surface area.
The conductances per unit area and the capacitance per unit area could be
multiplied by A to obtain the absolute conductances and capacitance for the whole
cell, but A would cancel out in the numerator and denominator of the equation for
.
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
( )
I ( , )
y y y
V t g y V = E , where the dynamics of the gating particle y are
first-order, i.e., 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 is
shown in the figure above. It is known that the Nernst equilibrium potential
.
( y V )
50 mV
y
E = +
From the results of the voltage-clamp experiment, find the values of , and
L
g
L
E
y
g .
There are three unknowns, so we must construct three simultaneous equations from
the voltage-clamp results. These are based on the ionic current equation:
( ) ( )
L y L L y y
I I I g V E g y V E = + = +
evaluated for three different time points in the experiment.
For , , 0 t <
3
60 10 V V

= 0 A I = and 0.3 y = , and therefore:
( ) ( )
3 3
0 60 10 0.3 60 10 50 10
L L y
g E g

= +
3
.
At , , and 0 t =
3
0 10 V V

=
9
27 10 A I

= 0.3 y = , and therefore:
( ) ( )
9 3
27 10 0 0.3 0 50 10
L L y
g E g

= + .
At , , and 99 ms t
3
0 10 V V

=
9
13 10 A I

= 1 y = , and therefore:
( ) ( )
9 3
13 10 0 1 0 50 10
L L y
g E g

= + .
Solving these three equations simultaneously gives:
330 nS,
100 mV,
400 nS.
L
L
y
g
E
g
=
=
=

8. Consider an action potential that is approximated by the rectangular spatial
waveform shown below.

The fiber has a radius of 4 m a = and an axoplasm conductivity of
0.02 S/cm
i
= .
Find the strength and location of the equivalent (lumped) sources.
The first spatial derivative of the rectangular transmembrane potential waveform
consists of two scaled delta functions located at 0 x = and 10 cm. Consequently, the
equivalent (lumped) sources will consist of (lumped) dipole sources at these two
locations.
From Eqn. (8.24), a lumped dipole source has the strength:
( ) ( )
2
1 2
,
i m m
D a v x v x =

where
1
x and
2
x define the spatial region over which the dipole source densities are
integrated.
Thus, the dipole source at has the strength: 0 cm x =
( ) ( )
( ) [ ]
2
1
2
4
0 0
4 10 cm 0.02 S/cm 0 mV 90 mV
0.90 nA cm,
i m m
D a v v

=

=
=

and the dipole source at has the strength: 10 cm x =
( ) ( )
( ) [ ]
2
2
2
4
10 10
4 10 cm 0.02 S/cm 90 mV 0 mV
0.90 nA cm.
i m m
D a v v

=

=
= +

9. Consider a chloride ion channel in a cell with an intracellular chloride
concentration of [ ] Cl 4
i
=
[
0 mM and an extracellular concentration of
] Cl
e
= 556 mM. The cell is at a temperature of 0C
f. Find the Nernst equilibrium potential for chloride.
g. If the transmembrane potential of the cell is presently at 70 mV, is
there a net efflux of chloride ions through this channel or a net influx?
m
V =
a. The temperature 0C corresponds to an absolute temperature of 273 K T =

, and
chloride has a valences of
Cl
1 Z = . For the ionic concentrations given above, the
chloride Nernst equilibrium potential is:
[ ]
[ ]
Cl
Cl
Cl
8.314 273 40
ln ln 61.9 mV
Cl 1 96487 556
i
e
RT
E
Z F

= = =

.
b. For 70 mV, the membrane potential is lower than the Nernst potential for
chloride, so from Eqn. (3.28) the current is negative, which corresponds to a net
efflux of chloride ions (because of their ve charge). The physical interpretation
is that the concentration difference tends to cause an influx of chloride ions
(diffusion), but a membrane potential below the Nernst potential creates enough
drift to overcome the diffusion and cause a net efflux of chloride ion.
m
V =
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 =
c. The transmembrane potential is:
( ) ( )
Na Na K K
rest
Na K
0.1 55 mV 0.8 90 mV
73.89 mV
0.1 0.8
g E g E
V
g g
+ +
= = =
+ +
.
Note that the transmembrane potential is independent of the cell surface area
2
4 A r =
4 5 m

. The conductances per unit area could be
multiplied by A to obtain the absolute conductances for the whole cell, but A
would cancel out in the numerator and denominator of the equation for .
( )
2
6
3.142 10 cm
= =
2
rest
V
d. For a current injected into the intracellular space of a cell with
membrane surface area
6 2
, the current density is:
inj
15.7 pA I =
A 3.142 10 cm =
inj 2
6 2
15.7 pA
5A cm .
3.142 10 cm
I
A

= =

Thus, the membrane equation in the steady-state is:
[ ] [ ]
( ) ( )
inj
K K Na Na
6 3 3 3 3
d
A d
5 10 0.8 10 90 10 0.1 10 55 10 0,
m
m m m
m m
I
V
g V E g V E C
t
V V

= + +

= + +

giving the steady-state transmembrane potential:
( ) ( )
3 3 3 3
3 3
0.8 10 90 10 0.1 10 55 10 5 10
0.8 10 0.1 10
68.33 mV.
m
V

+ +
=
+
=
6

Note that an equivalent formulation is to use the absolute current
and multiply the conductances per unit area by the membrane surface area to
obtain the total conductances for the entire membrane, i.e.:
inj
15.7 pA I =
[ ] [ ]
inj K K Na Na
d
d
m
m m
V
I g A V E g A V E C
t
= + +
m
.
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 = .
Substituting the equations for n
and
n
into ( ) d d
n
n t n n
= gives:
( )
( )
( )
d
d
1
1 ,
n
n
n n
n n
n
n n
n n
n n n
n n
n n n
t
n
n
n
n n
+
=
+

= +

+

= +
=

which is the standard HH formulation.
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 :
c. What are the relative conduction velocities of the two cables?
d. What are the relative input resistances of the two cables?
e. What are the relative space constants of the two cables?
f. What are the relative time constants of the two cables?
a. For an unmyelinated axon the propagation velocity is proportional to
1
2
i
R
.
Consequently, the conduction velocity
2
for axon #2 relative to the conduction
velocity
1
for axon #1 is:
,1 ,1
2
1 ,2 ,1
1
2
i i
i i
R R
R R
= = 0.7071 = .
b. The input resistance of a semi-infinite cable is
m i
r r . The input resistance of an
infinite cable is half of this, so the relative input resistances are the same as for a
semi-infinite cable:
,2 ,2 0,2
0,1 ,1 ,1
m i
m i
r r Z
Z r r
= .
For a cylindrical cable of diameter : d
2 2
4 4
m i m
m i 3
i
R R R
r r
d d d
= =
R
,
and consequently:
,2 ,1 0,2
0,1 ,1 ,1
2
i i
i i
R R Z
Z R R
= = 1.4142 = .
c. Assuming a negligible extracellular resistance (i.e., 0
e
r ), the space constant is:
4
m
i
d R
R
= ,
and consequently:
,1 ,1
2
1 ,2 ,1
1
2
i i
i i
R R
R R
= = 0.7071 = .
d. The time constant is dependent only on the membrane resistance and capacitance
m
m m m m m
R
r c C d R C
d

, not the axoplasmic resistivity, so the time

constant
2
= = =

of axon #2 relative to the time constant
1
of axon #1 is
2 1
1 = .
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, 0.4135 cm c = and 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 .
To determine the transmembrane currents resulting from the spatial waveform, we
make use of the cable equation for the transmembrane currents:
2
2
1
m
m
i e
v
i
r r x
=
+
,
which is valid for both linear and nonlinear cables.
The first and second spatial derivates in the regions 0 x < and are zero.
In the region 0 1 , the first and second spatial derivates are:
1.5 cm x >
.5 c x m
2
3
402.15 2 2 2 2
e sin 402.15 e 2sin cos
2 2 2
e sin 1.685 10 cos 972.55sin
m x c x c
x c
v
x x x
x c d d d d
x x x
d d d

= +

=

and
2
2
2
2 2
1 402.15 2 2 2 2
402.15 4 1 2 2 2 2 2 2
e sin 402.15 e 2sin cos
e sin cos e cos e sin ,
m x c x c
x c x c x c
c c d d d d
d c d d d d d d
v
x x x
x
x x x

= +

x

+ +

respectively, as shown in the figure below.
0 0.5 1 1.5
0
50
100
v
m

(
m
V
)
0 0.5 1 1.5
200
0
200
400
v
m
/
x

(
m
V
/
c
m
)
0 0.5 1 1.5
2000
0
2000
4000
x (cm)
2
v
m
/
x
2

(
m
V
/
c
m
2
)

Dividing the second spatial derivate by the sum of the intra- and extra-cellular
resistances per unit length gives the transmembrane current per unit length as a
function of
m
i
x shown in the top panel of the figure below.
To obtain the intra- and extra-cellular axial currents
i
I and
e
I , respectively, we make
use of the cable equations:
;
i e
m m
I I
i i
x x

= =

,
which are valid for both linear and nonlinear cables. These can be integrated over x
to give
i
I and
e
I as being equal to
1
m
i e
v
r r x
+
and
1
m
i e
v
r r x
+
, as plotted in the
middle and bottom panels, respectively, of the figure below.
0 0.5 1 1.5
2
0
2
4
i
m

(
A
/
c
m
)
0 0.5 1 1.5
0.5
0
0.5
I
i

(
A
)
0 0.5 1 1.5
0.5
0
0.5
x (cm)
I
e

(
A
)

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?
a. For an unmyelinated axon of diameter d , the propagation velocity is proportional
to d . Consequently, the conduction velocity
2
for cable 2 ( )
relative to the conduction velocity
1
2
10 m d =
for cable 1 (
1
5m d = ) is:
2 2
1 1
10
1.4142
5
d
d
= = = .
b. The input resistance of a semi-infinite cable is
m i
r r . The input resistance of an
infinite cable is half of this, so the relative input resistances are the same as for a
semi-infinite cable:
,2 ,2 0,2
0,1 ,1 ,1
m i
m i
r r Z
Z r r
= .
For a cylindrical cable of diameter : d
2 2
4 4
m i m
m i 3
i
R R R
r r
d d d
= =
R
,
and consequently:
( )
( )
( )
( )
( )
( )
3 2 3 2 3 2
0,2 2 1
3 2 3 2 3 2
0,1
1 2
5
0.3536
10
Z d d
Z
d d
= = = = .
c. Assuming a negligible extracellular resistance (i.e., 0
e
r ), the space constant is:
4
m
i
d R
R
= ,
and consequently:
2 2
1 1
1.4142
d
d
= = .
d. The time constant:
m
m m m m m
R
r c C d R C
d

= = =
is independent of the fiber diameter, so the time constant
2
of cable 2 relative to
the time constant
1
of cable 1 is
2 1
1 = .
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 3m a = and an axoplasmic conductivity of
0.03S/cm
i
= .
a. Find the dipole source densities for the regions 0 x = to 12 cm and 12 x = to
18 cm.
b. Find the strength(s) and location(s) of the lumped monopole source(s).
a. The dipole source density is defined as:
2
.
m
i x
v
a a
x

=
`

In the region from to 12 cm, the slope of the spatial action potential
waveform is constant (see the figure on the next page), and consequently the
dipole source density is:
0 x =
( )
( )
( )
2
1
2
4
0.1 V
3 10 cm 0.03S/cm
12 cm
70.69 pA.
i x
x
x
V
a a
x
a
a

=
=

The slope of the spatial action potential waveform in the region from to 18
cm is also constant, and the dipole source density is:
12 x =
( )
( )
( )
2
2
2
4
0.1 V
3 10 cm 0.03S/cm
6 cm
141.37 pA.
i x
x
x
V
a a
x
a
a

=
=

b. Each lumped monopole source is determined by:
2
2
2
d .
b
a
x
m
i
x
v
M a x
x

=

The second spatial derivative of a triangular transmembrane potential waveform
consists of three scaled delta functions located at 0 x = , 12 and 18 cm, as
illustrated below.
Integrating around the scaled delta function at 0 x = cm gives the lumped
monopole source:
( ) ( ) ( )
0
2
4 3
1
0
3 10 cm 0.03S/cm 8.333 10 V/cm d
70.68 pA.
M x x
+

=
=

Integrating around the scaled delta function at 18 x = cm gives the lumped
monopole source:
( ) ( ) ( )
18 cm
2
4 3
3
18 cm
3 10 cm 0.03S/cm 16.667 10 V/cm 18 cm d
141.37 pA.
M x x
+

=
=

The lumped monopole source at 12 x = cm must be equal and opposite to the sum
of the positive monopoles:
( )
( )
2 1 3
70.68 141.37
212.05 pA.
M M M = +
= +
=

0 6 12 18
0
50
100
V

(
m
V
)
0 6 12 18
20
0
20
V
/
x

(
m
V
/
c
m
)
0 6 12 18
20
0
20
x (cm)
2
V
/
x
2

(
m
V
/
c
m
2
)

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,
K
E and
Na
E , respectively?
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 ?
a. The temperature 24 C corresponds to an absolute temperature of

Given the ionic concentrations from the table above, the potassium and sodium
273 24 297 K T = + =
[ ]
[ ]
K
K
K K
8.314 297 400
ln ln 76.6 mV
1 96487 20
i
e
C
RT
E
Z F C

= = =

,
and
[ ]
[ ]
Na
Na
Na Na
8.314 297 50
ln ln 55.7 mV
1 96487 440
i
e
C
RT
E
Z F C

= = =

,
respectively.
b. The resting transmembrane potential is then:
( ) ( )
K K Na Na
rest
K Na
0.8 76.6 0.2 55.7
50.22 mV
0.8 0.2
g E g E
V
g g
+ +
= = =
+ +
.
c. Thus at rest the potassium and sodium current densities are:
[ ] ( )
3 3 3
K K rest K
0.8 10 50.22 10 76.6 10 21.184 A cm I g V E

= = =

2
,
and
[ ] ( )
3 3 3
Na Na rest Na
0.2 10 50.22 10 55.7 10 21.184 A cm I g V E

= = =

2
,
respectively.
The potassium current is positive, which corresponds to an efflux of potassium
ions, and the sodium current is negative, which corresponds to an influx of
sodium ions.
d. For a current
2
inj
5A cm I = injected into the intracellular space, the membrane
equation is:
[ ] [ ]
( ) ( )
inj K K Na Na
6 3 3 3 3
d
d
5 10 0.8 10 76.6 10 0.2 10 55.7 10 0,
m
m m m
m m
V
I g V E g V E C
t
V V

= + +

= + +

( ) ( )
3 3 3 3
3 3
0.8 10 76.6 10 0.2 10 55.7 10 5 10
0.8 10 0.2 10
45.1mV.
m
V

+ +
=
+
=
6

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 ( ) increase
when
c
V was increased from 30 mV
at 1 ms t
to ~ 0 mV?
c. Why did the peak amplitude of the early inward current decrease when
was increased from ~ 0 mV to 40 mV
c
V
+ ?
d. What is the approximate threshold potential
thr
V of this axon?
e. If the early inward current is carried by sodium, what is the approximate
sodium equilibrium potential
Na
E for this axon?
f. If the late outward current is carried by potassium and for this
axon, why is there no reversal of the late outward current in any of these
measurements?
K
65 mV E
a. Because this current turns on instantaneously and does not vary with time, it must
be the leakage current in the HH model.
b. This is produced by activation of this ion channel more open channels
increased conductance increased current.
c. Over this range of voltages, the conductance does not change much, but the
membrane potential approaches the ions Nernst equilibrium potential
decreased current.
d. The voltage-gated currents turn on somewhere between 40 and 30 mV, so
.
thr
35 mV V
e. The early current reverses somewhere between +40 and +60 mV, so
.
Na
50 mV E +
f. The potassium current activates somewhere above 30 mV, so the potassium
channels are all closed at the potassium reversal potential of , and
consequently no potassium current reversals are observed.
K
65 mV E
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 .
a. The time of the peak is determined by taking the first derivative of ( )
syn
g t w.r.t.
time and finding the time at which the derivate is equal to zero:
( )
peak peak
peak peak
syn
peak
peak
peak
peak
peak
d
const
const 0
d
0
1 0
0
.
t t t t
t t t t
g t
t
e e
t t
t
e e
t
t
t
t t
t t

= =
=
=
=
=

b. At time
peak
t t = , the conductance is:
( )
peak peak
syn peak peak
peak
const
,
t t
g t t t e
g
= =
=

and therefore:
1
peak peak
1
peak
peak
const
const .
t e g
g e
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
syn
E were equal to 20 mV, would the
synapse be excitatory or inhibitory? Briefly explain why.
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 = =
a. This synapse is excitatory because
syn rest
E V > , and consequently an increase in
( )
syn
g t from its resting value of zero will depolarize the membrane, bringing it
closer to its threshold potential.
b. If
syn
E were equal to 20 mV, the synapse would still be excitatory, because the
synaptic equilibrium potential would still be above the resting transmembrane
potential.
c. When there is no synaptic input, the time constant is:
6 12
90 10 90 10 8.1 ms RC

= = = .
d. When , the time constant is: ( )
syn peak
10 nS g t g = =
12
in
9
in
peak 6
90 10
4.26 ms
1 1
10 10
90 10
C C
R C
G
g
R
= = = = =
+ +
.
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,
K
E and
Na
E , respectively?
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 ?
a. The temperature 40 C corresponds to an absolute temperature of

Given the ionic concentrations from the table above, the potassium and sodium
273 40 313 K T = + =
[ ]
[ ]
K
K
K
8.314 313 150
ln ln 62.1 mV
K 1 96487 15
i
e
RT
E
Z F

= = =

,
and
[ ]
[ ]
Na
Na
Na
8.314 313 10
ln ln 69.2 mV
Na 1 96487 130
i
e
RT
E
Z F

= = =

,
respectively.
b. The resting transmembrane potential is then:
( ) ( )
leak K K Na Na leak leak
rest
K Na leak
leak
1.0 62.1 0.05 69.2 0.3
1.0 0.05 0.3
58.64 0.3
54 mV,
1.35
E g E g E g E
V
g g g
E
+ + + +
= =
+ + + +
+
= =

and consequently the Nernst equilibrium potential for the leakage channel is:
( )
leak
1.35 54 58.64
47.53 mV.
0.3
E
+
= =
c. Thus at rest the potassium, sodium and leakage current densities are:
[ ] ( )
3 3 3
K K rest K
1.0 10 54.0 10 62.1 10 8.1A cm I g V E

= = =

2
,
[ ] ( )
3 3 3
Na Na rest Na
0.05 10 54.0 10 69.2 10 6.16 A cm I g V E

= = =

2
,
and
[ ] ( )
3 3 3
leak leak rest leak
0.3 10 54.0 10 47.53 10 1.94 A cm I g V E

= = =

2
.
respectively, giving a net ionic current of
K Na leak
0 I I I + + = .
The potassium current is positive, which corresponds to an efflux of potassium
ions, and the sodium current is negative, which corresponds to an influx of
sodium ions. The leakage current is negative, but the valence of the charge
carrier(s) is unknown, so it may correspond to a net influx of cations or a net
efflux of anions.
d. For a current
2
inj
4 A cm I = injected into the intracellular space, the membrane
equation in the steady-state is:
[ ] [ ] [ ]
( ) (
( )
inj K K Na Na leak leak
6 3 3 3
3 3
d
d
4 10 1.0 10 62.1 10 0.05 10 69.2 10
0.3 10 47.53 10 0,
m
m m m m
m m
m
V
I g V E g V E g V E C
t
V V
V

= + + +

= +

+ +

)
3

( ) ( ) ( )
3 3 3 3 3 3
3 3 3
1.0 10 62.1 10 0.05 10 69.2 10 0.3 10 47.53 10 4 10
1.0 10 0.05 10 0.3 10
57.0 mV.
m
V

+ +
=
+ +
=
6

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

Assume:
i. the dendrite with the excitatory synapse can be modeled by an infinite
uniform cable with a radius of 1m a = and an intracellular resistivity of
; 187 cm
i
R =
ii. the extracellular axial resistance is negligible, i.e., 0
e
r ;
iii. the membrane specific resistance is
2
and the membrane
specific capacitance is
10 k cm
m
R =
2
1F cm
m
C = ;
iv. the threshold potential at the soma is 25 mV above the resting membrane
potential; and
v. synaptic input can be approximated by a step current injection that
causes a steady-state depolarization of 30 mV
m
v = at the site of the
synapse.
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 m 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?
a. This excitatory synapse acts like an intracellular current injection at the site of the
synapse on the dendrite. For an infinite cable with space constant , the spatial
decay of the steady-state relative transmembrane potential from the point of
current injection can be described by:
0
e ,
m
x
v v

=
where is the steady-state relative transmembrane potential at the point of
current injection, in this case 30 mV, and
0
v
x is the distance from the site of the
current injection.
For the parameter given above, the dendrite has a space constant of:
4 3
1 10 10 10
0.0517 cm 517 m.
2 0 2 187
m m
i e i
r aR
r r R

= = = = =
+ +

Consequently, the threshold potential will be equalled or exceeded by the steady-
state relative transmembrane potential for all values of x that satisfy:
0 thr
e
e
0.0517
0.0517
5
6
5
6
5
6
e
30e 25
e
0.0517
0.0517
0.0094 cm or 94 m.
log
log
m
x
x
x
v v v
x
x
x

Therefore the synapse needs to be within 94 microns of the soma in order for an
action potential to be generated.
b. The time constant of the dendrite is:
10 1 10 ms.
m m
R C = = =
Thus, at a distance from the synapse, the temporal response of the
membrane to a step current injection is given by:
40 m x =
( )
0
40 517
40 517
40 m, e 1 erf
2 2
e 1 erf mV
2
40 10
15 e 1 erf
2 517 10
40 10
e 1 erf m
2 517 10
x
m
x
v x t
v x t
t
x t
t
t
t
t
t
= =

V,

where t is in units of ms.
This function reaches a value of 25 mV at 14.17 ms t = , which is a little greater
than the membrane time constant of 10 ms.
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 6 m a = and an axoplasmic conductivity of
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.
a. The dipole source density is defined as:
2
A,
m
i x
v
a a
x

=
`

where is in units of cm, a
i
is in units of mS/cm and
m
v x is in units of
mV/cm.
The first spatial derivate of the action potential waveform is:
( )
peak peak
peak
2
2 2
2
277.1 138.55 mV cm
138.55 2 mV cm,
m
x x x x
x x
v
x e x e
x
x x e

=

as shown in the middle panel of the figure below.
Consequently, the dipole source density function is:
( )
( )
( )
peak
peak
peak
2
7
2
2
2
138.55 2 A
3.6 10 20 138.55 2 A
3.13 2 nA.
i x
x
x
x x
x x
x x
a x x e a
x x e a
x x e a

=
=
=
`

This dipole density function has a region of negative dipoles (i.e., pointing to the
left, away from the AP peak) from 0 x = to 2 cm and a region of positive dipoles
(i.e., pointing to the right, away from the AP peak) for see the curve
for
2 cm x >
m
v x in the figure below.
b. The monopole source density is defined as:
2
2
2
A cm,
m
i
v
I a
x

=
`

i
2
2
m
v x is in units of
mV/cm
2
.
The second spatial derivate of the action potential waveform is:
( )
peak peak
peak peak
peak peak peak
peak
2
2
2 2
2 2
2 2
2 2
2 2
2 2 2
2
277.1 277.1
277.1 138.55 mV cm
277.1 554.2 138.55 mV cm
138.55 2 4 mV cm ,
m
x x x x
x x x x
x x x x x x
x x
v
e x e
x
x e x e
e x e x e
x x e

+
= +
= +

as shown in the bottom panel of the figure below.
Consequently, the monopole source density function is:
( )
( )
( )
peak
peak
peak
2 2
7 2
2
2
2
2
138.55 2 4 A cm
3.6 10 20 138.55 2 4 A cm
3.13 2 4 nA cm.
i
x x
x x
x x
I a x x e
x x e
x x e

= +
= +
= +
`

This monopole density function has two regions of positive monopoles (i.e.,
sources) from to 0.586 cm & cm from and a region of negative 0 x = 3.414 x >
monopoles (i.e., sinks) from 0.586 x = to 3.414 cmsee the curve for
2 2
m
v x
in the figure below.
c. Each lumped dipole source is determined by:
( )
2 2
i i
a v x
i
( )
2
1
1 2
d A cm,
x
m
m m
x
v
D a x v x
x

= =

where is in units of cm, a is in units of mS/cm and is in units of mV.
m
v
The negative lumped dipole, corresponding to the dipole density region from
to and pointing in the
1
0 x =
2
2 cm x = x direction, has the strength:
( ) ( )
[ ]
1 2
A c
75 A c
m
v x

2
7
m
3.6 10 20 0 m
1.70 nA cm.
N i m
D a v x

=
=
=

The positive lumped dipole, corresponding to the dipole density region from
to and pointing in the
1
2 cm x =
2
x = x + direction, has the strength:
( ) ( )
[ ]
1 2
A c
5 0 A c
m
v x

2
7
m
3.6 10 20 7 m
1.70 nA cm.
P i m
D a v x

=
=
= +

d. Each lumped monopole source is determined by:
2
2
d A,
b
a
b a
x
m
x x
x
x x
v
M a x
x

= =

= =

2 2 m m
i i
v v
a
x x

i
m
v x is in units of
mV/cm.
The first positive lumped monopole, corresponding to the monopole density
region from to 0
a
x = 0.586 cm
b
x = , has the strength:
[ ]
2
1
7
A
3.6 10 20 63.89 0 A
1.44 nA.
b a
m m
i
x x
x x
v v
M a
x x

= =

=

=
=

The negative lumped monopole, corresponding to the monopole density region
from to 0.586 cm
a
x = 3.414 cm
b
[ ]
2
2
7
A
3.6 10 20 22.01 63.89 A
1.94 nA.
b a
m m
i
x x
x x
v v
M a
x x

= =

=

=
=

The second positive lumped monopole, corresponding to the monopole density
region from to 3.414 cm
a
x =
b
( )
2
3
7
A
3.6 10 20 0 22.01 A
0.50 nA.
b a
m m
i
x x
x x
v v
M a
x x

= =

=

=

=

0 2 4 6 8 10 12
0
25
50
75
v
m

(
m
V
)
0 2 4 6 8 10 12
100
50
0
50
100
v
m
/
x

(
m
V
/
c
m
)
0 2 4 6 8 10 12
0
250
x (cm)
2
v
m
/
x
2

(
m
V
/
c
m
2
)

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., ) and an
excitatory synaptic input causes the excitatory conductance to step
instantaneously from to
rest m
V V =
E
0 nS g =
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
m
V reach the threshold
potential
th
V ? Is this time shorter or longer than the resting membrane time
constant?
b. If an inhibitory synaptic input arrives at the same time as the excitatory
input and causes an instantaneous step in the inhibitory conductance
I
g , how
large does
I
g need to be to prevent the membrane potential
m
V from ever
reaching the threshold potential
th
V ?
a. The steady-state membrane potential for an excitatory synaptic input alone is:
( )
( )
E E rest
E
1
1
20 20 12.5 60
mV
20 12.5
10.77 mV.
m
R
R
g E V
V t
g
+
=
+
+
=
+
=

The membrane potential will move from its initial value of towards its new
steady-state with a time constant of:
rest
V
12
9 9
in E
3
1
70 10
s
20 10 12.5 10
2.15 10 s or 2.15 ms.
R
C C
G g
= = =
+ +
=

The temporal response of the membrane potential is consequently given by:
( ) ( )
( )
rest rest
2.15
1
10.77 60 1 60 mV,
t
m
t
V t V V e V
e

= +

= +

where t is in units of ms.
This function reaches the threshold potential
th
40 mV V = at , which
is substantially shorter than the resting time constant of:
1.13 ms t =
6 12 3
80 10 70 10 s 5.6 10 s or 5.6 ms. RC

= = =
b. The steady-state membrane potential for simultaneous excitatory and inhibitory
inputs is:
( )
( ) ( )
E E I I rest
E I
I
I
1
1
20 20 80 12.5 60
mV,
20 12.5
m
R
R
g E g E V
V t
g g
g
g
+ +
=
+ +
+ +
=
+ +

where is in units of nS.
I
g
To prevent action potential generation, the steady-state membrane potential must
be less than the threshold potential of 40 mV, so must satisfy:
I
g
( )
( ) ( )
I
I
I
20 20 80 12.5 60
40 mV
20 12.5
23.75 nS.
m
g
V t
g
g
+ +
= <
+ +
>


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1.

, not the axoplasmic resistivity, so the time

, and potassium and sodium both have valences of Z = +1.

, and potassium and sodium both have valences of Z = +1.

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