Appendix A
Voltages, potentials, and cell membranes
inside outside
Figure A1.1
Equilibrium potential
This state would be reached if
only one ion was able to cross
the membrane. Ions flow from
strong to weak concentration,
building electric charge on the
membrane.
At equilibrium, flow rates in
both directions match with
unequal concentrations on
either side, because
electrostatic forces make it
harder to flow from inside to
out, and easier to flow from
the outside in.
166
Membrane potential
A membrane potential is an electrical voltage that can be measured across the membrane of a cell.
Membrane potential is usually expressed as the voltage of the inside of the membrane compared
to the outside, in the same way that the 9 volts of a battery is the voltage difference between its
two terminals. Voltages are called potentials because they have the potential to drive electric
currents and do work.
The membrane potential in neurons is determined by differences in the concentration of sodium and
potassium ions between the inside and outside of the cell. The differences in concentration are
created by the ability of the membrane to tightly control the movement of ions into or out of the cell.
Neurons use metabolic energy to draw potassium ions into the cell and push sodium ions out. The
result is that potassium is about thirty times more concentrated inside than outside, and sodium
is about ten times more concentrated outside than inside.
There are three types of membrane potential–the equilibrium potential, the resting potential, and
the action potential. The next section will deal with each of these in turn.
Equilibrium potential
Equilibrium potential refers to the membrane voltage that would balance inward and outward
flow rates for one particular kind of ion. Every kind of ion (sodium, potassium, chloride, sulfate,
calcium, etc.) has its own equilibrium potential, which depends only on its concentration inside
and outside the cell. For example, potassium ions pass through membrane channels in both
directions with relative ease, but the rate at which they leak out is much greater due to the
concentration difference (high inside and low outside). Each potassium ion that leaves the cell will
carry positive charge with it, leaving a net negative charge behind. As more potassium ions leave
the cell, charge builds up on the membrane: positive outside as the potassium ions accumulate,
but negative inside because potassium ions have been lost. The separated charges cling tightly to
the insulating membrane, electrically attracting each other, and set up an electrical potential (or
voltage) across the membrane.
As the voltage increase builds, this potential makes it difficult for more potassium ions to travel
outward, toward the positively charged side. At the same time, it becomes easier for potassium
ions traveling inward, since they are heading toward negative charge. When the membrane
potential reaches a certain value, the outward flow slows and the inward flow increases so much
that they balance each other, and the cell stays in a steady state with a steady voltage on the
membrane. This voltage is called the equilibrium potential for that particular ion. Other ions have
different concentrations inside and out, so their equilibrium potentials would be different.
The equilibrium potentials for other ions depend on concentrations inside and outside the cell,
and the charge of the individual ions. Sodium would therefore reach its equilibrium potential
when positive voltage inside the membrane slowed its rate of inward leakage and increased its
Appendix A–Voltages, potentials, and cell membranes
outward leakage. Every kind of ion has an equilibrium potential, but whether the cell membrane
actually moves toward that equilibrium depends on whether that kind of ion can pass through.

Resting membrane potential

If all the ions were free to leak across the membrane, they would flow from the concentrated side
inside outside
to the dilute side, so that potassium would leak out of the neuron and sodium would flow in to
the neuron. However the membrane prevents them from doing so, except through specialized
openings (channels), which are selective for each type of ion. At any given moment the membrane
potential is influenced by which ions are able to pass through and carry charges across; as
channels open and close, the membrane potential moves toward the equilibrium potential of
whichever ions pass through most easily.
+
In a steady state, neuron membranes are permeable to potassium, which makes membrane
voltage move toward the potassium equilibrium potential. However, other ions, including sodium,
can also cross the membrane, even though their movement is more restricted. As the membrane Figure A1.2
Resting potential
approaches the potassium equilibrium potential, the tiny rate of inward sodium leakage increases
In the resting cell, multiple ion
and brings positive charge in, altering membrane potential the other way. The net result is that types continuously cross the
the resting membrane potential is close to the potassium equilibrium potential, but does not quite membrane through leak
reach it. This mix between the potassium and sodium equilibrium potentials is determined by the channels. None of them are at
membrane permeability for each ion. This also means that the inward and outward flows do not equilibrium, so active pumping
is required to maintain
balance for either ion, meaning that there is a steady loss of potassium and a steady gain of concentrations against the
sodium. The net result is that the cell has to burn energy to pump ions to maintain concentrations. steady leakage. Membrane
potential stabilizes in between
the equilibrium potentials for
Action potential each ion, according to leakage
rates.
With potassium channels open in the steady state, the membrane potential stays near the
equilibrium potential for potassium, with a negative charge inside the membrane and a positive
charge on the outside. Specific triggers can activate mechanisms that open sodium channels,
causing the membrane potential to move rapidly toward the sodium equilibrium, for a brief
inside outside
period of time. This brief, clear signaling event is known as an action potential.

Because sodium ions are maintained with the opposite concentration difference–weak
concentration inside, stronger concentration outside–opening sodium channels will push the
membrane potential the opposite way, toward positive charge inside and negative outside. Because
the amount of charge required is very small, and moves only a few nanometres, these changes can
occur very rapidly. Neurons and muscle cells exploit this by creating a brief, sharp flip between +

two states. This spike in voltage is used to trigger signaling at the synapses between neurons. To
achieve the flip, voltage-gated sodium channels need to open and close. In the signaling parts of
Figure A1.3
the axon, the membrane is studded with sodium channels, which open when the membrane
During action potential
potential reaches a certain threshold level. Opening these channels triggers a brief, time-limited
Although the large scale
reversal of membrane potential, which stops after just a millisecond or two. Potassium channels composition of the fluids
open briefly to restore the previous state. Because the process triggers a large voltage change, it inside and out remains almost
propagates itself in a spreading wave that races across the membrane, like a Mexican wave in a the same, changes in
permeability allow sudden
stadium crowd. freedom for sodium ions to
cross the membrane. This
Many descriptions of the action potential focus on the movement of ions. They focus on ions
causes a brief reversal of the
rushing in and out of ion channels, ions being pumped by membrane mechanisms, and so on. membrane potential toward
However, the simplest way to think about action potentials is to note that the established the sodium equilibrium.

The Brain Watson Kirkcaldie Paxinos 167


Figure A1.3 A cerebellar Purkinje cell
concentration differences of potassium
and sodium will set up opposing
equilibrium potentials, which are the
extremes of the range of membrane
potential in a normal neuron. The
actual, moment-to-moment membrane
potential varies within this range
according to which channels are open.
The threshold for triggering an action
potential is a fixed voltage determined
by the properties of voltage-gated
channels. The events leading to an
action potential can be summarized as
follows:

1. At rest, the (negative) potassium

equilibrium potential dominates.

2. Excitatory transmitters open

A cerebellar Purkinje cell that has been filled with
dye shows the extensive dendritic branching
characteristic of this cell type. (Adpated from an
image courtesy of CCDB, National Center for
Microscopy and Imaging Research, University of
California, San Diego).
sodium channels, so the membrane
potential moves a little way toward
the positive sodium equilibrium
potential. Since this means moving
from a negative membrane polar-
ization toward zero, this is termed
‘depolarization.’
3. If this takes the membrane potential
past threshold, many more sodium
channels open and the membrane
potential jumps much closer to the
sodium equilibrium potential; this
creates a voltage spike.

4. After this, the sodium channels are abruptly closed, and potassium channels are opened, so
membrane potential jumps back to the negative potassium equilibrium.

5. All the channels are reset and the cell returns to the resting, potassium-dominated state.

Many ions other than potassium and sodium also move in or out of the cell during these
processes, but the main point to grasp is that the sodium-potassium pump works to keep the
equilibrium potentials stable and the cell operating consistently. Note that inhibitory transmitters
hyperpolarize the membrane (they increase the negative charge inside the cell) and make the
production of an action potential less likely.

168 Appendix A–Voltages, potentials, and cell membranes