Neurophysiology – lecture 3

January 13, 2011

1 Review:
1. The analysis of neuronal function will start with the smallest components: molecules and ions.
(a) The Neuron Doctrine states that neurons (all cells) are completely bounded by membranes.
(b) The major constituent of membranes are phospholipids.
(c) Phospholipids are composed of a polar head and 2 16-18 long hydrocarbon tails. These tails were
derived from fatty acids.
(d) Water molecules are more attracted to the partial charges on other water molecules than they are
to the nonpolar tails of the phospholipids. As a result water molecules are excluded from between
these hydrocarbon tails and the hydrocarbon tails wind up aggregating together to form the lipid
bilayers that characterize membranes.
(e) These lipid bilayers also exclude ions and other charged molecules and hence are impermeable to
many ions and molecules.
2. As an explanatory devise we will use Hydraulic Models to explain the functioning of Electrical Models
which in turn provide good descriptions of the behavior of cell membranes.
(a) In the Hydraulic Model work (energy) must be done on a pump to cause fluid to flow through a
sequence of tubes.
(b) In the Electrical Model electrical energy obtained from a battery is needed to cause charged
electrons to flow around a circuit of wires. Electrical energy is described as “voltage”, more
properly “voltage difference” and equals the amount of work required to move a unit of charge
dq
from one point to another. The movement of charge is termed a “current” and equals .
dt
(c) Consideration of the Hydraulic Model in Figure 1B explains why “Current only flows in closed
circuits”.

2 The Concept of Resistance

1. (a) The constriction shown in the tubing of the Hydraulic Model of Figure 1D left restricts the amount
of fluid that can flow through the tube at any given pressure as compared to the amount that can
flow through a tube without a constriction.
(b) Therefore to pump an equal volume of fluid through the constricted tube as can be pumped
though the tube lacking a constriction in the same period of time a greater force must be applied
to the pump plunger.

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 (c) Since F × ∆s = work, it appears that more work must be done on the volume of fluid in the pump
to obtain the same flow of fluid.
(d) With the even narrower opening for fluid passage shown in the Hydraulic Model of Figure 1E
even more work must be done on the fluid volume in the pump to obtain the same flow of fluid
as seen through the tube that has no constriction.
(e) In each case the flow rate increases linearly as the work done on the fluid in the pump increases.
The greater the hindrance to the flow of fluid the greater is the amount of work required to achieve
a given flow of fluid.
2. (a) The analog of the constriction in the tube of the Hydraulic Model is called a “resistor” in the
Electrical Model and is diagramed as a short sawtooth section in an otherwise straight wire.
(b) In the right hand section of Figure 1D what effect will the resistor have on the current driven
through the closed loop circuit?
(c) As in the Hydraulic Model, more work must be done on each unit of charge to move the same
amount of charge through the wire containing the resistor as compared to a wire not containing
a resistor.
(d) And if an even larger resistor is incorporated into the circuit then an even larger amount of work
must be done on each unit of charge to obtain the same rate of charge flow or current, I.
(e) Again the rate of charge flow or I is linearly proportional to the amount of work/unit charge
with the slope of this linear relationship varying as the size of the resistor varies. The larger the
resistor in the circuit the less I is obtained for a given amount of work/unit charge expended by
the battery, i.e., voltage difference.
(f) Any linearly proportional relationship can be converted into an equation by inserting a constant
into the relationship, so ∆V = I × constant. In this case the constant is called the “resistance”
and signified by an “R” or “r”.
(g) This insertion produces Ohms Law of electricity,∆V = I×R. We use this relationship to determine
∆V
the resistance of patches of membrane, cells, etc. by solving for R = where R is quantified
I
in ohms which are signified by the symbol Ω.
(h) The resistance of a copper wire is very close to 0 Ω because the electrons are relatively free to
move from one atom to another.
(i) Similarly the ions in a salt solution, say Na+ and Cl− , are mobile and hence the resistance of the
solution is very low.

3 Application of these concepts to neurons

1. Clean membranes have a very high affinity to glass! This is fortunate because it allows very small glass
tubes to be inserted into cells after which the cell membrane becomes bound to the glass thus sealing
up the hole created in the membrane by the insertion of the glass tube.
2. Glass microelectrodes were first developed in 1949 by Ling and Gerard who softened a segment of glass
capillary tubes over a flame and then rapidly pulled the ends of the tube apart until the tube broke
apart. The needle-like ends of these tubes could be pulled to be less than 0.5 µm in diameter (less than
1/200th the thickness of a human hair). Surprisingly, the hole in the middle of the capillary was not
sealed off in this process, only made to be very, very small. These pointed capillary tubes could then
be filled with a concentrated salt solution so that electricity can be conducted from the sharp end of

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 the capillary to the other end. This arrangement is now referred to as a “sharp microelectrode” and
can be used to record from the interior of cells after the cell membrane has sealed around the shank of
the penetrating microelectrode.
3. More recently beginning in 1976, investigators have carefully heated the tips of such microelectrodes
causing the tip to melt slightly and be opened up to a diameter of 1-2 µm which when filled with an
electrolyte solution is referred to as a “patch electrode.” For recordings the rounded leading surface
of a patch electrode is maneuvered into contact with the surface of a neuron or muscle fiber and a
slight suction is applied to the contents of the patch electrode which draws a small area of the cells
membrane up into the electrode without breaking the membrane. In this position the cells membrane
binds to the interior glass wall of the patch electrode forming a very high resistance seal referred to as
a “gigaohm seal”.
4. Gigaohm = 109 Ω = GΩ, megaohm = 106 Ω = MΩ, kilohm = 103 Ω = kΩ.
5. The small patch of membrane attached to the end of the patch electrode can be pulled free from the
rest of the cell without being disrupted. By passing current through it and noting the change in voltage
produced by this passage of current it is calculated that such a membrane patch has a resistance larger
than 100 GΩ. So it does not allow many ions to flow through it even though the membrane is only 2
molecules thick.
6. This high resistance is a very important property of lipid membranes which is essential for their ability
to generate action potentials and other types of potential.

4 Figure 2 C
1. From some patches of membrane positioned at the end of patch electrodes small steps in current are
seen. The small current steps recorded in this figure are about 3 pA.
coulomb of charge
2. Current is of course measured in amperes. 1 Ampere = 1 . We will talk about
second
milliamperes = mA = 10−3 A,
microamperes = µA = 10−6 A,
nanoamperes = nA = 10−9 A,
and picoamperes = pA = 10−12 A.
So 3 pA isnt very much current, but obviously can be recorded.
3. Properties of these small steps in current recorded across the small piece of membrane attached to the
patch electrode:
(a) The current steps are always about the same amplitude, in this case 3 pA.
(b) Their duration varies.
(c) When they will occur and when they will not be seen is not very predictable.