When two or more ions contribute to the membrane potential across the plasma membrane (V_m) of a cell, it is likely that the membrane potential would not be at the equilibrium potential (V_eq.) for any of the contributing ions. Thus, no ion would be at its equilibrium (i.e., V_eq. ≠ V_m). For example, the resting membrane potential of a typical neuron is neither at the K⁺, Na⁺, nor Cl⁻ equilibrium potential (see figure). This means that at the resting potential, K⁺, Na⁺, and Cl⁻ are not at electrochemical equilibrium and, thus, the chemical and electrical forces acting on K⁺, Na⁺, and Cl⁻ are not equal. When an ion is not at its equilibrium, an electrochemical driving force (V_DF) acts on the ion, causing the net movement of the ion across the membrane down its own electrochemical gradient. The driving force is quantified by the difference between the membrane potential and the ion equilibrium potential (V_DF = V_m − V_eq.). The driving force is the net electromotive force that acts on the ion. The magnitude of the driving force indicates how far the membrane potential (V_m) is from the electrochemical equilibrium (V_eq.) of an ion. Thus, the magnitude of the driving force indicates how far an ion is from its equilibrium. The arithmetic sign (i.e., positive or negative) of the driving force acting on an ion along with the knowledge of the valence of the ion (i.e., cation or anion) can be used to predict the direction of ion flow across the plasma membrane (i.e., into or out of the cell). See Table 1 below.

Table 1 summarizes how the arithmetic sign of the driving force may be used to predict the direction of ion flow across the plasma membrane (i.e., into or out of the cell). For cations (positively charged ions such as Na⁺, K⁺, H⁺, and Ca²⁺), a positive driving force (i.e., V_DF > 0) predicts ion movement out of the cell (efflux) down the ion's electrochemical gradient, and a negative driving force (i.e., V_DF < 0) predicts ion movement into the cell (influx). The situation is reversed for anions (negatively charged ions such as Cl⁻ and HCO₃⁻), where a positive driving force predicts ion movement into the cell (influx), and a negative driving force predicts ion movement out of the cell (efflux). If the membrane potential (V_m) is exactly at the equilibrium potential (V_eq.) for an ion (V_m = V_eq.), the driving force acting on the ion would be zero (V_DF = 0). If V_m = V_eq., it can be seen that V_DF = V_m − V_eq. = 0. In this case, the ion is said to be in electrochemical equilibrium, and there would be no net movement of the ion across the plasma membrane into or out of the cell (i.e., no net flux of ion).

Using the information provided in Table 1 and the equilibrium potential for any given ionic species, you should be able to determine the direction of flow for that ion at a given membrane potential. For example, assume that V_K = −90 mV, and V_m = −65 mV. Thus, the driving force acting on K⁺ is: DF_K = −65 − −90 = +25 mV. The sign of the driving force is positive. Since K⁺ is a positively charged ion (cation), a positive value for the driving force indicates that K⁺ is flowing out of the cell (under these conditions).

As a second example, assume that V_Cl = −65 mV. Using the same reasoning, you should be able to conclude that if V_m = −65 mV, there would be no net movement of Cl⁻ into or out of the cell. The driving force acting on Cl⁻ here is DF_Cl = −65 − −65 = 0 mV. It should be intuitive that if the membrane potential is at the equilibrium potential for an ion, no net force acts on the ion (i.e., driving force = 0), and there will be no net movement of the ion across the plasma membrane. Indeed, in many cells, the contribution of Cl⁻ to the membrane potential is small and V_Cl usually (but not always) follows V_m (i.e., Cl⁻ distributes across the membrane to adjust the inside concentration to establish a V_Cl that is close to V_m). While in these cases, Cl⁻ may not contribute greatly to the resting membrane potential, the existing Cl⁻ permeability does guard against large changes in the membrane potential. As we will see in future lectures, this is extremely important in excitable cells such as neurons.

You should use the electrochemical driving force calculator to perform additional calculations for K⁺, Na⁺, and Cl⁻ at a variety of membrane potentials until it becomes second nature to you and you begin to intuitively appreciate how the driving force influences the net movement of cations and anions across the plasma membrane.