The cell membrane maintains a separation of charge, establishing an electrical difference across its surface known as the resting membrane potential (RMP). This potential is a fundamental property of nearly all cells, especially neurons and muscle cells, which use it for signaling. When the cell is in a resting state, the interior is consistently negative relative to the outside environment. This negative charge typically measures around -70 millivolts (mV) in a neuron, though the exact value can vary by cell type. The negative charge inside the cell results from highly regulated forces that control the movement and distribution of charged particles.
How Ion Concentration Gradients Are Established
The electrical charge across the membrane is entirely dependent on the unequal distribution of specific ions between the intracellular and extracellular fluids. The main players in this process are the positive ions, or cations, potassium (\(K^+\)) and sodium (\(Na^+\)), and the negative ion, or anion, chloride (\(Cl^-\)).
Within the cell’s cytoplasm, the concentration of potassium ions is kept very high, while the concentration of sodium and chloride ions is relatively low. Conversely, the outside of the cell is characterized by a high concentration of sodium and chloride ions. This creates strong concentration gradients for each ion, meaning the chemical driving force pushes \(K^+\) out of the cell and both \(Na^+\) and \(Cl^-\) into the cell.
The concentrations are substantial: \(K^+\) can be 20 to 30 times more concentrated inside the cell than outside, while \(Na^+\) is typically 10 to 14 times more concentrated outside than inside. The cell membrane acts as a selective barrier, allowing these concentration differences to persist.
The Critical Role of Potassium Leak Channels
The primary reason the cell interior becomes negative is the selective permeability of the membrane to potassium ions at rest. The cell membrane is studded with numerous non-gated channels, often called two-pore domain \(K^+\) leak channels, that remain continuously open. These channels allow \(K^+\) to move freely across the membrane, while the membrane is nearly impermeable to \(Na^+\) and other ions in the resting state.
Potassium ions follow their powerful chemical gradient, moving from the high concentration inside the cell to the low concentration outside. Since \(K^+\) carries a positive charge, its movement out of the cell removes positive charge from the interior, leaving behind unbalanced negative charges.
This \(K^+\) efflux does not continue indefinitely until concentrations are equalized; it quickly creates an electrical force that opposes the chemical force. As the inside becomes more negative, this electrical potential begins to pull the positive \(K^+\) ions back into the cell. The net outward movement of \(K^+\) ceases when the electrical force pulling \(K^+\) in balances the chemical force pushing \(K^+\) out, a point known as the potassium equilibrium potential, which is typically around -90 mV.
The Sodium-Potassium Pump Sustains the Charge
While the selective movement of potassium ions establishes the negative potential, active transport is required to maintain the necessary concentration gradients over long periods. This task falls to the sodium-potassium pump, an enzyme known as \(Na^+/K^+\) ATPase. The pump uses energy derived from ATP to move ions against their concentration gradients.
For every molecule of ATP consumed, the pump actively transports three \(Na^+\) ions out of the cell and simultaneously brings two \(K^+\) ions back into the cell. This specific exchange ratio is essential because it directly counters the slow, steady leakage of \(Na^+\) into the cell and \(K^+\) out of the cell that occurs even at rest. The necessary high-internal \(K^+\) and high-external \(Na^+\) gradients are continuously maintained.
The pump also makes a small, direct contribution to the negative resting potential because it is electrogenic, meaning it moves a net charge across the membrane. By expelling three positive charges (\(Na^+\)) and only importing two positive charges (\(K^+\)), the pump removes one net positive charge from the cell with every cycle. This contributes perhaps -5 mV to -10 mV to the total negative potential, reinforcing the charge separation established by \(K^+\) leakage.
The Influence of Impermeable Negative Proteins
A final, structural factor contributing to the negative internal charge is the presence of large, negatively charged molecules trapped inside the cell. The cytoplasm contains a high concentration of organic anions, which include proteins, amino acids, and organic phosphates. These macromolecules are far too large to pass through the cell membrane or its ion channels.
Because these negative charges are fixed and cannot follow the positive ions that diffuse out, they provide a constant source of negative potential inside the cell. When \(K^+\) ions leak out, the remaining negative charge on these trapped proteins and molecules immediately creates the electrical attraction that pulls \(K^+\) back toward the cell interior. Without these fixed negative charges, the cell would lack the necessary counter-ions to establish a stable, negative electrical potential.