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  All cells under resting conditions have an electrical potential difference across the plasma membrane such that the inside of the cell is negatively charged with respect to the outside. This potential is the resting membrane potential; its magnitude depends on the type of cell, but usually ranges between -60 and -90 mV. By convention 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
The membrane potential can be accounted for by the fact that there is a slightly greater number of negative charges than positive charges inside the cell and a slightly greater number of positive charges than negative charge outside. The excess negative charges inside the cell are electrically attracted to the excess positive charges outside the cell, and vice versa.
Thus, these excess ions collect along a thin shell on the inner and outer surfaces of the plasma membrane, whereas the bulk of the intracellular and extracellular fluid is electrically neutral. The total number of positive and negative charges that have to be separated across the membrane to account for the potential is an insignificant fraction of the total number of charges actually in the cell.

The resting membrane potential is determined mainly by two factors:

  • the differences in ion concentration of the intracellular and extracellular fluids and

  • the relative permeabilities of the plasma membrane to different ion species.

Sodium, potassium, and chloride ions are present in the highest concentrations and therefore generally play the most important roles in the generation of the resting membrane potential.

Ion Extracellular
Na+ 150 15
Cl- 110 10
K+ 5 150
The sodium and chloride ion concentrations are lower inside the cell than outside, and the potassium concentration is greater inside the cell.
These concentration differences for sodium and potassium are due to the action of a membrane active transport system which pumps sodium out of the cell and potassium into it.
The Na+ - K+ Pump Cycle
A. Three Na+ ions on the inside of the cell membrane bind to the pump protein (carrier molecule).

B. The pump protein is phosphorylated by ATP.

C. The 3 Na+ ions are released to the outside of the cell membrane, and the outside K+ binds to the pump protein.

D. K+ is released to the inside of the cell and the pump protein releases the phosphate and returns to its original conformation.



To understand how the concentration differences for sodium and potassium (maintained by the membrane pumps) create membrane potentials, let us consider the following situation: let us assume that the membrane is permeable only to potassium but not to sodium. Therefore, potassium can diffuse through the membrane but sodium cannot. Initially there is no potential difference across the membrane because the two solutions are electrically neutral; i.e., they contain equal numbers of positive and negative ions.
Inside --> Outside

Because the membrane is permeable to potassium ions, they will flow down their concentration gradient; i.e. towards the outside of the cell. There is also a concentration gradient favouring sodium diffusion in the opposite direction but the membrane is not permeable to sodium. Accordingly, after a few potassium ions have moved out of the cell, the cell will have an excess of negative charge, whereas the outside solution will have an excess of positive charge; i.e., a potential difference will exist across the membrane.

Inside --> Outside
The potential difference itself influences the movement of potassium ions. They (being positive) are attracted by the negative charge on the intracellular side of the membrane and are repulsed by the positive charge on the extracellular side of the membrane. As long as the force due to the concentration gradient driving potassium ions outside the cell is greater than the electrical force driving it in the opposite direction there will be net outside movement of potassium ions; the cell will become more and more negative until the electric force opposing the exit of potassium ions outside of the cell equals the force due to the concentration gradient favouring its exit.
Inside --> Outside
The membrane potential at which the electrical force is equal in magnitude but opposite in direction to the concentration force is called the equilibrium potential for that ion. At the equilibrium potential there is no net movement of the ion because the opposing forces acting on it are exactly balanced.
Inside --> Outside


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