In living cells, the resting membrane potential (V_m) is seldom governed by only one ion such as K⁺, Na⁺, Cl^-, etc. If this were the case, the membrane potential could be predicted by the equilibrium potential (V_Eq.) for that ion, and could be easily calculated by using the Nernst equation. Instead, the membrane potential is generally established as a result of the relative contributions of several ions. In many cells, K⁺, Na⁺, and Cl^- are the main contributors to the membrane potential. For example, in a typical mammalian neuron, K⁺, Na⁺, and Cl^- contribute to a resting membrane potential of around -70 mV, a membrane potential value that is not at the equilibrium potential for K⁺, Na⁺, or Cl^-. This is because in neurons at rest, there are K⁺-, Na⁺- and Cl^--selective channels in the plasma membrane. These selective ion channels allow K⁺, Na⁺, and Cl^- to each move down its own electrochemical gradient. The movement of any ion down its own electrochemical gradient will tend to move the membrane potential toward the equilibrium potential for that ion. Therefore, the transmembrane movements of all three ions (K⁺, Na⁺, and Cl^-) collectively contribute to the membrane potential. When more than one ion channel is present (and open) in the plasma membrane, the membrane potential can be calculated by using the Goldman-Hodgkin-Katz equation (GHK equation).

Enter appropriate values in all cells except the one you wish to calculate. Therefore, at least ten cells must have values, and no more than one cell may be blank. The value of the blank cell will be calculated based on the other values entered. After a calculation is performed, the calculated cell will be highlighted and subsequent calculations will calculate the value of the highlighted cell (with no requirement to have a blank cell). However, a blank cell has priority over a highlighted cell.

As mentioned above and as can be seen from the GHK equation shown above, the value of the membrane potential is determined by the concentration gradients and the relative permeability values of ions for which there are open channels in the plasma membrane. The physiological concentration gradients are homeostatically maintained within a very narrow range. The magnitude of the permeability (i.e., how many open channels in the plasma membrane) for any given ion can, in fact, be regulated physiologically, and determines the relative contribution of that ion to V_m. It is important to remember that the movement of any ion down its own electrochemical gradient will tend to move the membrane potential toward the equilibrium potential for that ion. The larger the permeability of a given ion, the larger the contribution of that ion will be in setting the membrane potential. For example, by examining the GHK equation, it can be seen that if p_K is much larger than p_Na and p_Cl, V_m will be closer to the equilibrium potential for K⁺ (V_K) than it will be to the equilibrium potential for Na⁺ (V_Na) or Cl^- (V_Cl), although it will never be exactly at V_K unless both p_Na = 0 and p_Cl = 0. As another example, if p_Na is very large compared to p_K and p_Cl, V_m will be closer to V_Na, although it will never be exactly at V_Na unless both p_K = 0 and p_Cl = 0. Notice that if the channels for a certain ion are all closed (i.e., the permeability for that ion is zero), the GHK equation is reduced and simplified to include only the terms regarding the other two ions.