Mouse vs. Scorpion

Mouse vs. Scorpion

A Tale Of Venom And Action Potentials

by Justin F. Shaffer Department of Chemical and Biological Engineering Colorado School of Mines, Golden, CO

Learning Objectives

• Compare and contrast the structures and functions of neurons and glia.

• Explain how ion channels contribute to membrane potential.

• Explain how action potentials are generated and propagated.

• Predict how membrane potential and action potentials may be altered by foreign substances.

Our Cast of Characters

Arizona Bark Scorpion

• Lives in Sonoran Desert of US Southwest.

• Most venomous scorpion in North America. 

• Venom causes intense pain in humans for 24 – 72 hours. In rare cases can cause death.

Southern Grasshopper Mouse

• Lives in Sonoran Desert of US Southwest

• Feeds almost entirely on arthropods, such as beetles and grasshoppers 

• Occasionally eats smaller mice

Multiple Choice

Who do you think would win in a showdown?

Let's do an experiment

FACT: When mice feel pain on a part of their body, they lick that part

EXPERIMENT: Researchers injected bark scorpion venom into the hind paws of the common house mouse and the southern grasshopper mouse; As a control, they injected 0.9% saline solution. Then they measured how long they licked their paws afterwards.

What data do you think they observed?

Multiple Choice

What data do you think they observed?

How is this possible?

​We'll return to this question shortly...

And Now For Something A Little Different

But we'll return to the mouse...

Recall the glorious neuron...

Multiple Choice

What is true about this image?

• The image shows only a neuron

• The image shows only glia

• The image shows both a neuron and glia

Multiple Choice

Action potentials travel through which structure?

• Dendrites

• Axon

• Schwann Cells

• Axon Terminal

Multiple Choice

Of the following, what is the major contributor to a neuron's resting membrane potential of about -70 mV?

• Diffusion of sodium ions through ungated sodium channels.

• Diffusion of potassium ions through ungated potassium channels.

• Diffusion of sodium ions through voltage-gated sodium channels.

• Diffusion of potassium ions through voltage-gated potassium channels.

Recall the neuron membrane...

• Which side has more potassium ions? More sodium ions?

• Which side is more negatively charged? Positively charged?     

Hyperpolarization – membrane potential becomes more negative.

​

Depolarization – membrane potential becomes less negative.

Multiple Choice

What would happen if this ungated sodium channel was blocked?

• The neuron would hyperpolarze

• The neuron would depolarize

Phases of the Action Potential

Now we are talking about voltage-gated channels and NOT ungated channels!

1 - Resting potential

2 - Partial Depolarization

3 - Na+ Channels Open (Depolarization)

4 - Repolarization - K+ Channels open, Na+ channels close

5 - Hyperpolarization - K+ channels close

Multiple Choice

In what stage do voltage-gated Na+ channels open?

• Stage 1

• Stage 2

• Stage 3

• Stage 4

• Stage 5

Multiple Choice

In what stage do voltage-gated K+ channels open?

• Stage 1

• Stage 2

• Stage 3

• Stage 4

• Stage 5

And now, back to the scorpion and the mouse...

Let's do another experiment

Researchers injected bark scorpion venom into mouse neurons and measured how many action potentials were generated after the venom was introduced.

Multiple Choice

Based on these data, what effect do you think the venom is having on the grasshopper mouse neurons?

• The venom is only blocking voltage-gated sodium channels.

• The venom is only blocking voltage-gated potassium channels.

• The venom is opening voltage-gated sodium channels or blocking voltage-gated potassium channels.

• The venom is opening voltage-gated potassium channels or blocking voltage-gated sodium channels.

What effect does the venom have on the grasshopper mouse?

• These neurons transmit pain signals (action potentials) to the grasshopper mouse brain.

• The venom blocks pain sensations in the grasshopper mouse.

One last experiment

Researchers injected increasing amounts of bark scorpion venom into mouse neurons and measured the flow of sodium ions (current) across the cell membrane.

Multiple Choice

Which conclusion about the effects of venom on the grasshopper mouse is supported by these data?

• The venom is only blocking voltage-gated sodium channels.

• The venom is only blocking voltage-gated potassium channels.

• The venom is opening voltage-gated sodium channels.

• The venom is opening voltage-gated potassium channels.

Why is the grasshopper mouse is resistant to the venom of the bark scorpion?

There are two missense mutations in a specific voltage-gated sodium channel in the grasshopper mouse genes E859Q and Q862E.

The venom binds to the mutant sodium channel and blocks its function.