What primarily determines the resting membrane potential?

The resting membrane potential is primarily determined by the passive diffusion of potassium (K) ions across the cell membrane. This phenomenon occurs because the membrane is more permeable to K ions than to other ions when the cell is at rest. The concentration gradient for potassium, which is higher inside the cell and lower outside, drives K ions to move out of the cell. This outflow causes the inside of the cell to become relatively more negative compared to the outside, creating the resting membrane potential.

While active transport mechanisms, such as the Na+/K+ ATPase pump, also play a significant role in maintaining the concentration gradients of sodium (Na) and potassium, their contribution is not as direct in establishing the resting potential at a specific moment in time. Instead, it is the selective permeability and the resulting passive diffusion that predominantly set the resting membrane potential. Other ions, such as chloride (Cl) and calcium (Ca), do not contribute as significantly to the resting potential in most cells compared to the role of potassium. This focus on potassium dynamics highlights why its passive diffusion is considered the primary determinant of the resting membrane potential.