Membrane potential is the voltage difference across the membrane, with the interior typically being

• A. More positive than the exterior.
• B. More negative than the exterior.
• C. Neutral relative to the exterior.
• D. The interior is more negative relative to the exterior.

Answer: (D)

Membrane potential arises from charge separation across the cell membrane, and at rest the inside of the cell is more negative than the outside. This negativity comes from ion gradients and selective permeability. The membrane is more permeable to potassium than to other ions, so K+ tends to leak out down its gradient. As positive charges leave, the inside becomes depleted of positive charge and enriched in negatively charged proteins and other anions that can’t cross the membrane. The Na+/K+ pump also contributes by moving three Na+ ions out for each two K+ ions brought in, which favors a more negative interior. Because of these factors, the interior maintains a negative voltage relative to the exterior, rather than being neutral or positive.