Pre-class preparation exercise: The excitable cell

During class on Wednesday February 10th, Thursday February 11th, and Tuesday February 16th,
you will be exploring how nerve cells (neurons) work. On these three class days, you will be
analyzing a series of molecular models, graphs, and equations to deepen your understanding of
how cells generate and transmit electrical signals. Use this document to familiarize yourself with
the models and equations, so you can work efficiently in class.
To begin: Biologists use the word model to refer to graphics or equations or statements that
represent a hypothesis or set of hypotheses about how some aspect of the world works. In
Bio180, you were introduced to Mendels model of inheritance, which was a series of
statements about how alleles are transmitted from parents to offspring. In Bio200, you were
introduced to the double-helical model of DNA structure, which was based on a physical
representation of a DNA molecules structure.
Its important to understand two key things about models: 1) they represent hypothesesoften
based on datathat are modified or thrown out as more information is discovered, and 2) all are
simplifications of reality. In creating a model, a scientists goal is to capture key aspects of what
is actually going on.
For example, the figure to the right is a model that was
published recently in a journal called Cell. The authors of this
paper are trying to summarize what is known about a signal
transduction pathway, called Hippo, that is involved in
immune responses to invading bacteria. The colored shapes
represent molecules (most are proteins); the black lines and
arrows represent phosphorylation events that inactivate or
activate proteins. If two shapes touch each other, it means
that they physically bind to each other.
You should be able to find the cartoony representation of
the plasma membrane, and infer that the shape labeled Tl
is a transmembrane receptor that triggers events inside the
cell when it binds a signal called Spz.
Some elements in this modelthe identity of the molecules
involved, whether they bind to each other, and whether they
get activated or deactivatedare based on data:.
But many aspects of this representationthe relative sizes
and locations of the molecules and their shapes and colors
are meaningless. There is also no information on how long
each interaction lasts or what conditions modify it, and its
likely that the molecules and interactions shown here are only a subset of the actual system.

The punchline is that models are not literalthey are devices that are meant to be useful in
advancing understanding. Now lets explore some of the models you encounter in learning
about electrical signaling.

1. Models of carriers and channels (passive transporters)

The models on the right represent three different types of
membrane proteins that are involved in facilitated
diffusionmeaning, the energetically favorable
movement of ions or molecules that otherwise would not
cross a membrane readily, because of their size or
charge.
In each case, the artist is showing cross sections of a
protein, using yellow to indicate hydrophobic regions and
green to indicate hydrophilic regions. The cartoony shapes are fanciful or roughly based on
data about the actual form of the protein.
The protein on the far right is a channel is particularly important in electrical signaling, as it
allows potassium ions (K+) to cross membranes.

2. Models of membrane pumps (active transporters)

The sodium-potassium pump, or Na+-K+ ATPase, is another membrane protein that is critical
in electrical signaling. Here the artist is using the same color-coding as before, but showing
a series of static images to illustrate the concepts that a) sodium and potassium ions bind to
specific locations in the protein, b) ATP binds to a specific location and phosphorylates the
protein, and c) in response to phosphorylation, the protein changes shape in a way that
results in sodium ions being transported out and potassium ions being transported in.

3. Models of voltage-gated channels

The cartoon on the right is a model of the third type of
membrane transport protein that is critical in electrical
signaling: a voltage-gated channel. Here the artist is
trying to communicate that these proteins have regions
that act like flaps to open or close a channel through
the interior of the molecule. Specific ions, like sodium or
potassium, can move across the membrane when the
flaps are open. As youll learn, the flaps move in
response to changes in the voltage across the
membrane.

4. Equations as models
Dr. Daniel will also be introducing how the voltage
across a membrane can be calculated if the
concentrations of ions outside and inside the
membrane are known. The Nernst equation, on the
right, is a mathematical model that allows you to
do this.

RT Cin
E
ln
zF Cout

Like graphical models of membrane proteins or signal transduction pathways, an

equation attempts to capture key parameters and their relationships, and thus serve as a
relatively simple and useful way to make predictions for how changing conditions affect a
particular outcomein this case, membrane voltage.

And thats it! We hope this background will help you grasp the key concepts in electrical
signaling more efficiently.