What causes a cell to have a negative voltage on the inside relative to the outside?

• A. K+, Na+, and Ca++ ions
• B. Cl- ions only
• C. Water movement across the membrane
• D. ATP depletion inside the cell

Answer: (A)

The resting membrane potential is set by unequal ion distribution across the membrane and how permeable the membrane is to those ions. Potassium leaks out of the cell through its channels more readily than other ions, carrying positive charge out and making the inside negative. But the gradients and permeabilities of multiple ions shape the exact voltage, especially potassium, sodium, and calcium. The Na+/K+ pump helps maintain these gradients, but the negative interior at rest mainly reflects how these ions move across the membrane. Water movement isn’t the driver of the polarity, and ATP depletion would disrupt the gradients over time rather than establish the resting negativity.