1. The membrane Potential
There is an unequal distribution of charges across the membrane.
The inside of the cell is negatively charged compared to the outside.
This difference in charge is known as the membrane potential.
Membrane potential due to:-
1-The action of the N+/K+ pumps.

2. The effect of fixed anions on the distribution of cations.
2- Cellular proteins and the phosphate groups of ATP and other organic molecules are negatively charged at the pH of the cell cytoplasm (anions) are “fixed” within the cell. As a result, they attract positively charged inorganic ions (cations) from the extracellular fluid that can pass through channels in the plasma membrane.
The effect of fixed anions on the distribution of cations.

3. Because the plasma membrane is more permeable to K+ than to any other cation, K+ accumulates within the cell more than the others as a result of its electrical attraction for the fixed anions.
Potassium (K+) becomes more highly concentrated within the cell.
The intracellular K+ concentration is 150 mEq/L in the human body compared to an extracellular concentration of 5 mEq/L.
As a result of the unequal distribution of charges between the inside and outside of cells, each cell acts as a tiny battery with the positive pole outside the plasma membrane and the negative pole inside (potential difference).
Potential difference is of critical importance in physiological processes as muscle contraction, the regulation of the heart beat, and the generation of nerve impulses.

4. Equilibrium Potentials
The inorganic ions in the intracellular and extracellular fluid are maintained at specific concentrations.
Each ion contribution to the potential difference across the plasma membrane—or membrane potential —depends on:-
(1) Its concentration gradient.
(2) Its membrane permeability.
Because the plasma membrane is usually more permeable to K+ than to any other ion, the membrane potential is usually determined primarily by the K+ concentration gradient.

5. We can ask a hypothetical question: What would be the voltage of the membrane potential if the membrane were permeable only to K+?
The fixed anions would cause the intracellular K+ concentration to become higher than the extracellular concentration.
However, once the concentration gradient reached a particular value, net movement of K+ would cease.
Potassium equilibrium potential
If more K+ entered the cell because of electrical attraction, the same amount would leave the cell by net diffusion. (Equilibrium)

6. EK of K+ is – 90 millivolts (mV).
The membrane potential that would stabilize the K+ concentrations is known as the K+ equilibrium potential (EK) .
EK of K+ is – 90 millivolts (mV).
A sign ( + or – ) placed in front of the voltage always indicates the polarity of the inside of the cell.
Expressed in a different way, a membrane potential of – 90 mV is needed to produce an equilibrium in which the K+ concentrations are 150 mM inside and 5 mM outside the Cell.
Concentrations of ions in the intracellular
and extracellular fluids.

7. What would the membrane potential be if the membrane were permeable only to Na+?
The inside of the cell would have to be the positive pole, repelling the Na+ and causing its concentration to be lower inside than outside the cell.
Calculation reveals that an equilibrium potential of +66 mV, with the inside of the cell the positive pole, maintains the Na+ concentration of 12 mM inside and 145 mM outside the cell.
The ENa is thus written as +66 mV.
Equilibrium potentials are useful to know because they tell us what happens to the membrane potential when the plasma membrane becomes highly permeable to one particular ion.

8. Nernst Equation
The Nernst equation calculates equilibrium potential for a particular ion when its concentrations are known.
At a temperature of 37°C:
The equilibrium potential for a cation has a negative value when Xi is greater than Xo.

9. Resting Membrane Potential
Resting Membrane Potential is the membrane potential of a real cell that is not producing impulses.
If the plasma membrane were only permeable to Na+, its resting membrane potential would equal the ENa of + 66 mV.
if it were only permeable to K+, its resting membrane potential would equal the EK
of – 90 mV.
A real resting cell is more permeable to K+ than to Na+, but it is not completely impermeable to Na+.
As a result, its resting membrane potential is close to the EK but somewhat less negative due to the slight inward diffusion of Na+.
Since the resting membrane potential is less negative than the EK, there will also be a slight outward diffusion of K+.

10. 2- The specific permeability of the membrane to each different ion.
The actual value of the resting membrane potential depends on two factors:
1-The ratio of the concentrations( Xo/Xi) of each ion on the two sides of the plasma membrane.
2- The specific permeability of the membrane to each different ion.
Many ions—including K+, Na+, Ca2+ , and Cl−— contribute to the resting membrane potential.
Their individual contributions are determined by the differences in their concentrations across the, and by their membrane permeabilities.
The resting membrane potential. Because some Na+ leaks into the cell by diffusion, the actual resting membrane potential is not as negative as the K+ equilibrium potential. As a result, some K+ diffuses out of the cell, as indicated by the dashed lines.

11. Role of the Na+/K+ Pumps.
The resting membrane potential of most cells in the body ranges from – 65 mV to – 85 mV (in neurons it averages – 70 mV). (close to the EK because the resting plasma membrane is more permeable to K+ than to other ions)
Role of the Na+/K+ Pumps.
Since the resting membrane potential is less negative than EK, some K+ leaks out of the cell. The cell is not at equilibrium with respect to K+ and Na+ concentrations.
The concentrations of K+ and Na+ are maintained constant because of the Na+/K+ pumps.
The Na+/K+ pump transports 3 Na+ out of the cell for every 2 K+ that it moves in, it has the net effect of contributing to the negative intracellular charge.

12. As a result of Na+/K+ pumps activities, a real cell has:-
1- A relatively constant intracellular concentration of Na+ and K+.
2- A constant membrane potential (in the absence of stimulation) in nerves and muscles of – 65 mV to – 85 mV