ELEC ENG 3BB3 Cellular Bioelectricity

Solutions to Homework Assignment #2

1. The results of a voltage-clamp experiment are shown below.
30

40

0.9
45

0.8
0.7

50
50

0.6
0

50
100
Time (ms)

150

200
0.5

y(V)

V (mV)

35

0.4

0.3
0.2

I (nA)

0.1
14

70

60

50
40
V (mV)

30

0
20

21
50

50
100
Time (ms)

150

200

Assume that the measured transmembrane current I (V , t ) is comprised of a passive leakage

current I L (V ) = g L (V E L ) and a time- and voltage-dependent current I y (V , t ) = g y y (V E y ) ,

where the dynamics of the gating particle y are first-order, i.e., dy (V , t ) dt = ( y 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 E y = 70 mV .
a. Is the current I y (V , t ) activated by depolarization or hyperpolarization? Is I y (V , t ) an
inward or an outward current in the voltage-clamp experiment performed above?
b. From the results of the voltage-clamp experiment, find the values of g L , E L and g y .
(25 pts)
a. The asymptotic value of the activation particle y increases if the transmembrane potential is
made more positive, so the current I y (V , t ) is activated by depolarization. In the voltageclamp experiment, hyperpolarization of the membrane leads to a larger total inward current.
Because hyperpolarization causes deactivation of the current I y (V , t ) , it follows that this must
be an outward current. This can also be argued from the value of the equilibrium potential
because E y is more negative than the holding potentials used in the voltage-clamp experiment,
the term V E y must be positive, as are g y and y , so I y (V , t ) must be a positive, i.e., outward,
current.
Dr. Ian C. Bruce

March 8, 2005

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b. There are three unknowns, so we must construct at least three simultaneous equations from the
voltage-clamp results. These are based on the ionic current equation:

I = I L + I y = g L (V EL ) + g y y (V E y )
evaluated for at least three different time points in the experiment.
For t < 0 , I = 0 and y = 1 , and therefore:

0 = g L ( 30 103 EL ) + g y 1 ( 30 103 + 70 103 ) .

At t = 0 , I = 14 109 and y = 1 , and therefore:

14 109 = g L ( 50 103 EL ) + g y 1 ( 50 103 + 70 103 ) .

At t 99 ms , I = 21109 and y = 0.3 , and therefore:

21109 = g L ( 50 103 EL ) + g y 0.3 ( 50 103 + 70 103 ) .

At t = 100 ms , I = 14 109 and y = 0.3 , and therefore:

14 109 = g L ( 30 103 EL ) + g y 0.3 ( 30 103 + 70 103 ) .

Solving any three of these equations simultaneously gives:

g L = 200 nS,
EL = +70 mV,
g y = 500 nS.

Dr. Ian C. Bruce

March 8, 2005

Page 2 of 6

2. 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)

a. For an unmyelinated axon of diameter d , the propagation velocity is proportional to d .

Consequently, the conduction velocity 2 for cable 2 ( d 2 = 10 m ) relative to the conduction
velocity 1 for cable 1 ( d1 = 5 m ) is:

d2
2
10
=
=
= 1.4142 .
1
d1
5
b. The input resistance of a semi-infinite cable is rm ri . 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:
Z 0,2
=
Z 0,1

rm ,2 ri ,2
rm ,1ri ,1

For a cylindrical cable of diameter d :

rm ri =

Rm 4 Ri

=
d d2

4 Rm Ri
,
2d 3

and consequently:

Z 0,2 ( d 2 )
(d )
( 5) = 0.3536 .
=
= 1 32 =
32
3 2
Z 0,1 ( d1 )
( d2 )
(10)
3 2

32

32

c. Assuming a negligible extracellular resistance (i.e., re 0 ), the space constant is:

d Rm
,
4 Ri

and consequently:

d2
2
=
= 1.4142 .
1
d1
d. The time constant:

= rm cm =

Rm
C d = RmCm
d m

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 .
Dr. Ian C. Bruce

March 8, 2005

Page 3 of 6

3. Transmembrane currents measured in a squid axon from a voltage-clamp experiment are

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

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 Vthr 35 mV .
e. The early current reverses somewhere between +40 and +60 mV, so E Na +50 mV .
f. The potassium current activates somewhere above 30 mV, so the potassium channels are all
closed at the potassium reversal potential of EK 65 mV , and consequently no potassium
current reversals are observed.
Dr. Ian C. Bruce

March 8, 2005

Page 4 of 6

4. Consider the source-fiber geometry of Fig. 7.5 of Plonsey and Barr (shown on p. 8 of Lecture
#19), such that the extracellular potential is given by Eqn. (7.70):

e =

I0

4 e r

where r is the distance from the source to the fiber at the axial distance z from the middle of
the fiber. h is the distance between the source and the fiber where the source is
perpendicular to the fiber, i.e., at z = 0 .
Find:
a. the extracellular potential as a function of z , i.e., e ( z ) ,
b. the activation function

2e
,
z 2

c. the positions of the peaks of the resulting regions of initial depolarization and
hyperpolarization predicted by the activation function, stating which are a peak of
depolarization and which are peaks of hyperpolarization, and
d. the positions of the boundaries between the initial depolarized and hyperpolarized regions.
(25 pts)

a. The distance r from the electrode to the position z on the fiber is:
r = h2 + z2 .

Therefore the extracellular potential at position z on the fiber is:

e ( z ) =

I0

4 e

1
h + z2
2

b. The activation function

2e
is then:
z 2

e
I
z
= 0
z
4 e ( h 2 + z 2 )3 2

2
2
2
I 0 3z ( h + z )
2e
=
z 2 4 e ( h 2 + z 2 )5 2

Dr. Ian C. Bruce

I0

2 z 2 h2

4 e ( h 2 + z 2 )5 2

March 8, 2005

Page 5 of 6

c. The peaks of the activation function

2e
are located where its derivate equals zero:
z 2

3e
I 0 9 zh 2 6 z 3
=
=0
z 3 4 e ( h 2 + z 2 )7 2

9 zh 2 6 z 3

(h

+ z2 )

72

=0

9 zh 2 6 z 3 = 0
z 3 = 23 zh 2
z = 0,

3
2

h.

z = 0 is the location of the peak of the hyperpolarized region, and z =

3
2

h are the locations

of the peaks of the flanking depolarized regions.

d. The boundaries between the depolarized and hyperpolarized regions are located where the
activation function equals zero:
2e
I0
2 z 2 h2
=
=0
z 2 4 e ( h 2 + z 2 )5 2

2 z 2 h2

( h2 + z 2 )

52

=0

2z2 h2 = 0
z=

1
2

h.
h=1
0.2

0.2
0.4

e/z (normalized)

0.6
0.8
1
5

Dr. Ian C. Bruce

3/2 1/2 0 1/2 3/2

z

March 8, 2005

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