All cells under resting conditions have a potential difference across their plasma membranes with the inside of the cell negatively charged with respect to the outside. This potential is the resting membrane potential. By convention, extracellular fluid is assigned a voltage of zero, and the polarity (positive or negative) of the membrane potential is stated in terms of the sign of the excess charge on the inside of the cell. For example, if the intracellular fluid has an excess of negative charge and the potential difference across the membrane has a magnitude of 70 mV, we say that the membrane potential is -70 mV (inside relative to outside). The magnitude of the resting membrane potential varies from about -5 to -100 mV, depending upon the type of cell; in neurons, it is generally in the range of -40 to -90 mV. The resting membrane potential holds steady unless changes in electrical current alter the potential across the membrane.
The resting membrane potential exists because there is a tiny excess of negative ions inside the cell and an excess of positive ions outside. The excess negative charges inside are electrically attracted to the excess positive charges outside the cell, and vice versa. Thus, the excess charges (ions) collect in a thin shell tight against the inner and outer surfaces of the plasma membrane, whereas the bulk of the intracellular and extracellular fluids are neutral. The number of positive and negative charges that have to be separated across a membrane to account for the potential is an infinitesimal fraction of the total number of charges in the two compartments.
Each of ions of sodium, potassium, and chloride in the extracellular fluid and in the intracellular fluid of a typical nerve cell has a 10 to 30 fold difference in concentration between the inside and the outside of the cell. The membrane permeabilities to these ions are restricted, although to different degrees. Sodium and potassium generally play the most important roles in generating the resting membrane potential. Note that the sodium and chloride concentrations are lower inside the cell than outside, and that the potassium concentration is greater inside the cell. The concentration differences for sodium and potassium are established by the action of the sodium-potassium pump that pumps sodium out of the cell and potassium into it.
The magnitude of the resting membrane potential is determined mainly by two factors: (1) differences in specific ion concentrations in the intracellular and extracellular fluids, and (2) differences in membrane permeabilities to the different ions, which reflect the number of open channels for the different ions in the plasma membrane.