Neurophysiology – lecture 6

January 25 2011

1 Review:
1. To allow ions to enter or exit a cell ion channels must span the entire membrane.
2. The transmembrane (TMS) portion of ion channels must be composed of amino acids with lipophilic
side chains.
3. The lipophilic portions of the ion channels must contain sequences of lipophilic amino acids which are
18 - 21 amino acids long to span the membrane.
4. In voltage-dependent K+ channels there are 4 such 20 amino acid sequences in each channel subunit.
5. Ion channels are often identified because they have multiple TMS regions.
6. Functions of an ion channel:
(a) Form a water-filled pore through the membrane
(b) Have a sensor for transmembrane voltage or ligands or stretch.
(c) Are ion selective.
(d) They open and close -i.e. are “gated”.
7. Some channels are voltage-dependent the probability of their being open changes as the voltage differ-
ence across the membrane in which the channel is located changes.
(a) Since like charges repel and unlike charges attract it is likely that the voltage sensor in voltage-
sensitive channels contains amino acids with charged side chains.
(b) Every third amino acid in the 20 amino acid sequence of the 4th TMS of the K+ channel subunit
is a positively charged amino acid (lys or arg).
(c) These positively charged amino acids could all be on that same face of the alpha helix facing into
the water-filled pore.
(d) Removal of one of these 6 or 7 amino acids results in a channel which is less sensitive to changes
in transmembrane voltage and hence this alpha helix appears to be part of the channel voltage-
sensor.

2 Ion channels lipid membranes and the functioning of whole

cells
1. We will now move from the analysis of molecular function to the analysis of cellular function.

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 2. Our aim will be to generate an electrical model of a cell so we can better understand how cells work
electrically.
3. At present our model of a cell is that of a membrane surrounding some cytoplasm and in turn being
surrounded by extracellular fluid.
4. Handout Figure 5 is a table which lists the intracellular and extracellular ion concentrations in muscle
fibers.
5. From this table one should note that the intracellular concentration of cations (+) equals the intracel-
lular concentration of anions (-). Therefore the net charge inside the cell is approximately 0 coulombs.
6. This condition is a basic principle called electroneutrality.
7. We shall have to wait a while to see how this condition can be reconciled with the observation that
the inside of cells at rest is negatively charged relative to ground.
8. From the table we also note that most of the extracellular cations are Na+ and most of the extracellular
anions are Cl− . To simplify things we will consider that the extracellular fluid only contains Na+ and
Cl− .
9. Similarly most of the intracellular cations are K+ , but the intracellular anions are mostly proteins and
small organic anions. Cl− is present only in low concentration.
Therefore we will consider the intracellular ions to be only K+ and A− where A− stands for the sum
of the intracellular anions located on proteins and small organic molecules.
10. It was demonstrated that the introduction of ions into distilled water makes that water have a low
resistance, i.e., be a good conductor.
11. PRin ciple: Ions in solution are mobile which produces a low resistance, high conductance solution.
12. Therefore, in generating an Electrical Model of a cell we can consider that both the intracellular
cytoplasm and the extracellular medium are good conductors of electricity and can be represented in
the Electrical Model as wires.
13. On the other hand each small area of cell membrane provides a resistance to current flow through
the membrane. Since there are many small patches of membrane around the membrane, they must
be represented in the Electrical Model as many resistors placed in parallel to one and another and
connected to extracellular wire at one end and the intracellular wire at the other.
14. In this configuration these resistors are spoken of as “resistors in parallel”.
15. It is both tiresome and confusing to draw a lot of resistors in parallel. However, it is possible to
simplify this array of resistors in parallel and accurately represent it as a single resistor if the value
of that resistor is carefully chosen. Such a single resistor is called an “equivalent resistor” and is
designated Req.
16. Say we have an array of resistors in parallel, call them r1 , . . . , rn .
If we apply a current Itotal from a current source to one side of the array of parallel resistors and
remove it from the other side sending it back to the current source it is apparent that some amount of
this current will flow through each of the resistors. Let i1 be the current going through r1 and in be
the current flowing though rn .
n
X
Note that Itotal = i1 + . . . + in = ik . This satisfies the Law of the Conservation of Charge and
k=1
Kirchoffs Current Law.
∆V
Now if the voltage difference across this array of n parallel resistors is ∆V then i1 = r1

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 Then

n
∆V ∆V X ∆V
Itotal = + ... + = (1)
r1 rn i=1
ri

So it follows that

n
Itotal 1 1 X 1
= + ... + = (2)
∆V r1 rn r
i=1 i

Lastly

n
Itotal 1 X 1
= = (3)
∆V Req r
i=1 i

17. In summary resistors in parallel add by the “Inverse Law”.

18. So a distributed set of parallel resistors can be considered as a single equivalent resistor, Req , whose
value is determined by the “Inverse Law”.

3 Applying these principles to membrane resistance

1. As you will diagram for me while answeRin g Problem Set #1 problem 1 assume there are 2 intracellular
microelectrodes in a cell being bathed in physiological saline. Assume one microelectrode is attached
to an appropriately wired current source and the other is used to record intracellular voltage relative
to ground using a preamplifier.
2. When 1 nA is run through the “current electrode” the recorded intracellular voltage becomes more
negative by 10mV. This indicated there is a resistance between the end of the current electrode and
ground. This resistance is called the “input resistance” of the cell and is abbreviated Rin .

∆Vm 10 mV
Rin = = = 10 · 106 Ω = 10 MΩ (4)
I 1 nA
10 MΩ is a reasonable value for Rin but values for Rin vary widely from 100 KΩ to 400 GΩ as seen in
different types of cells, making Rin a not too useful measure.
3. Which would have a larger Rin – a large cell or a small one?
Answer: A small cell will have a larger resistance than a larger (other things being equal) because has
more current paths through its membrane than a small cell hence less current need flow along any one
of these paths through the local membrane resistance.
Therefore Rin will vary as cell size varies.
4. By contrast the resistance of a patch of membrane of a particular area should be much more constant
across cells, since all cell membranes look more or less alike. This resistance measure is called the
Specific Membrane Resistance and is designated Rm . Rm = the resistance of a unit area of cell
membrane.
So 1/Rin = Number of unit areas of membrane/Rm , by the Inverse Law and

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 Rin = Rm /Number of unit areas = Rm /Area of the cell membrane
Or Rm = Rin × Area of the cell membrane.
5. Values for Rm obtained by the above formula vary much less than those for Rin . Rm varies within the
range of 1 - 10 KΩ cm2 .
6. What is the source of this resistance?
A 1 cm2 membrane 0.1 mm thick of protein would have an Rm = 2 Ω cm2
A 1 cm2 membrane 0.1 mm thick of carbohydrate would have an Rm = 20 Ω cm2
A 1 cm2 membrane 0.1 mm thick of lipid would have an Rm = 20 GΩ cm2 .
So for a membrane to have such a high Rm lipid is the only macromolecule it could be made out of.