Overview of Membrane Potentials
Introduction
Although nerve cells are not firing when at rest, they are far from idle. Instead of simply waiting, they constantly use ATP to power membrane Na⁺/K⁺ pumps. The combination of these membrane pumps and K⁺ leak channels maintains a stable charge equilibrium across their membranes, called the resting membrane potential, which prepares the nerve to fire.
An action potential is a rapid and temporary disruption of the resting membrane potential that travels along the axon. The process begins when a threshold stimulus is reached and voltage-gated Na⁺ channels open, allowing Na⁺ to rush inward down its concentration gradient. The influx of Na⁺ briefly reverses the membrane potential, a process examined in detail in Exercise 2.
The Role of Na⁺/K⁺ Pumps
Protein pumps (ATPases) in the axon membrane use energy from ATP to move ions in and out of the cell. They pump three Na⁺ ions out for every two K⁺ ions they pump in.
As a result, Na⁺ accumulates outside the cell, and K⁺ accumulates inside, creating concentration gradients that represent stored potential energy. During an action potential, these gradients drive the sequential movement of Na⁺ and K⁺ ions across the cell membrane.

The Role K⁺ Leak Channels.
The resting membrane is much more permeable to K⁺ ions than to Na⁺ ions. As a result, many K⁺ ions that are pumped into the cell diffuse back out along their concentration gradient.
This loss of K⁺ ions causes the cell interior to become more negative relative to the exterior, establishing an electrical gradient and polarizing the membrane.

The Resting Equilibrium
The outward movement of K⁺ ions does not continue indefinitely. Instead, K⁺ is repelled by the growing positive charge outside the membrane and attracted to the increasingly negative charge inside.
Although the membrane is far less permeable to Na⁺, a small number of Na⁺ ions also leak into the cell down their concentration gradient. This inward movement of positive charge slightly offsets the loss of K⁺.
Eventually, the chemical and electrical forces acting on K⁺ balance. At this point, K⁺ ions continue to move in both directions, but there is no net movement. This state of dynamic equilibrium contributes to a stable resting membrane potential.

Learning Objectives
After completing this activity, you should be able to:
- Identify which ions are most concentrated inside and outside the cell at rest.
- Describe the resting membrane potential of a typical neuron and explain how it is measured.
- Identify the threshold level, peak membrane potential, and time course of an action potential.
Note: This simulation uses the Hodgkin-Huxley model with mammalian parameters at 37°C.
1. Before the recording electrode was inserted, the oscilloscope showed 0 mV. What does this tell you about what the oscilloscope is actually measuring?
2. Na⁺ is most concentrated outside the cell and K⁺ is most concentrated inside. What process is responsible for maintaining these concentration gradients?
3. The resting membrane potential is approximately −70 mV. What does the negative sign indicate about the charge on the inside of the membrane relative to the outside?
4. The action potential briefly reaches a positive membrane potential before returning to rest. Based on the ion gradients you observed, which ion do you think is responsible for this brief reversal? Explain your reasoning.
