Resting membrane potential
- Define membrane potential
- Describe how the resting membrane potential is developed and maintained
- Compare the distribution and permeability differences of ions across the cell membrane
- Describe how differences in ion distribution and permeability contribute to the resting membrane potential
- Explain the role of the Na+ –K+ ATPase pump in this process.
- Electrically neutral solutions are intracellular fluid and extracellular fluid, in that each has an equal number of ions charged positively and negatively. A simple but important concept is that each other is attracted to these opposite charges and ions of the same charge repel each other.
- A slight accumulation of negative charges-) (on the inner surface of the plasma membrane is attracted to an equal number of positive charges (+) that have accumulated on the outer surface of the membrane in an unstimulated or resting cell.
- Therefore, all cells are electrically polarised at rest; that is, relative to the outside, the inside of the cell is slightly negative. This charge separation across the plasma membrane is referred to as the potential of the membrane.
- The magnitude of the potential of the membrane is mainly dependent on the number of opposite charges separated by the membrane. The greater the charge separation then, the greater the potential of the membrane is.
- The potential is measured in millivolts ( mV) because the actual number of charges involved is quite small. In addition, the predominant charge on the internal surface of the cell membrane defines the sign (+ or-) of the potential.
- The membrane potential under resting conditions is, therefore, negative. For their functions, nerve cells and muscle cells rely on changes in this membrane potential. In other words, changes in the potential of the membrane convey information to these cell types.
Development of the resting membrane potential
- In a typical unstimulated neuron is approximately 70 mV of the resting membrane potential. The development of this potential depends on three ions’ distribution and permeability: (1) sodium(Na+); (2) potassium(K+); and (3)anions(A-).
- These ions are unevenly distributed across the plasma membrane between the intracellular fluid (ICF) and the extracellular fluid (ECF) and each has a different degree of permeability.
- Sodium ions are found in the ECF at a higher concentration and K+ ions are found in the ICF at a higher concentration; A- refers to large cell-only anionic proteins.
- Most mammalian plasma membranes are approximately 50 to 75 times more permeable to K+ions under resting conditions than they are to Na+ ions. At all times, the anions are impermeable.
- It is because of these underlying conditions that the potential for the resting membrane is generated and maintained. The motion of Na+ and K+ ions in and out of the cell, if permeable, depends on two factors:
- Concentration gradient
- Electrical gradient
- Consider a condition in which the membrane is only potassium-permeable. The K+ ions initially diffuse out of the cell down their concentration gradient because potassium is in a higher concentration inside the cell.
- As a consequence, an excess of these positively charged ions would accumulate along the plasma membrane’s external surface in the ECF. The impermeable A-ions will remain inside the cell along the inner surface of the plasma membrane, attracted to these positive charges.
- A negative membrane potential is created by this outward movement of positive charges because the inside of the cell is now negative relative to the outside. However, as the K+ ions that are positively charged continue to diffuse outward, an electrical gradient begins to develop that also affects the K+ ion diffusion.
- The K+ ions that have moved down their concentration gradient from the cell have caused the external surface of the membrane to accumulate an excess of (+) charges. Because these (+) charges would begin to repel any additional K+ ions as charges repel each other, and oppose the further movement of (+) charges outward.
- Alternatively, the positively charged K+ ions are now electrically drawn to the negatively charged A- ions that remain inside the cell. K+ ions not only diffuse outward down their concentration gradient at this point, but also diffuse down their electrical gradient into the cell.
- Eventually, the subsequent force that moved inward K+ ions exactly balances the initial force that moved outward K+ ions, so there is no further net potassium diffusion. At this point, the membrane potential has reached the equilibrium potential for K+ (EK+) and is equal to -90 mV.
- The membrane potential therefore approaches-90 mV when the permeability of the plasma membrane to potassium is high compared to that of sodium. Next, consider a condition in which the membrane is permeable only to sodium.
- As sodium is outside the cell in a higher concentration, the Na+ ions initially diffuse down their concentration gradient into the cell.
- As a result, an excess of these positively charged ions accumulates along the inner surface of the plasma membrane in the ICF; an excess of negative charges remains outside the cell along the plasma membrane ‘s external surface in the form of the impermeable extracellular anion, chloride (Cl–).
- A positive membrane potential is created by this inward movement of positive charges because the inside of the cell is now positive relative to the outside. However, as the Na+ ions that are positively charged continue to diffuse inwards, an electrical gradient develops once again.
- The (+) charges accumulated in the ICF are beginning to repel any additional Na+ ions and are opposed to further inward movement of (+) charges. Instead, the positively charged Na+ ions are now attracted to the Cl– ions remaining outside the cell that are negatively charged.
- Finally, the initial force moving Na+ ions inward down their gradient of concentration is precisely balanced by the subsequent force moving Na+ ions outward down their electrical gradient, so that there is no further net sodium diffusion.
- At this point, the membrane potential has achieved the equilibrium potential for Na+(ENa+) and is equal to +60 mV. Thus, when the sodium permeability of the plasma membrane is high compared to that of potassium, the potential of the membrane approaches +60 mV.
- The membrane potential is closer at any given time to the equilibrium potential of the more permeable ion. Na+ ions and K+ ions are permeable under normal resting conditions, but potassium is significantly (50 to 75 times) more permeable than sodium.
- A large number of K+ ions therefore diffuse outward, and a very small number of Na+ ions diffuse inward down their gradients of concentration.
- As a consequence, K+ ions’ comparatively copious external movement has a powerful impact on the value of the resting membrane potential, driving it towards its equilibrium potential of-90 mV.
- The slight inward motion of Na+ ions, however, which tends to drive the membrane potential towards its +60 mV equilibrium potential, makes the membrane potential slightly less negative.
- A typical neuron-resting membrane potential of-70 mV results from the balance of these two opposing effects. A vital role in this process is also played by the Na+-K+ pump. Three Na+ ions are pumped out of the cell into the ECF for each molecule of ATP expended, and two K+ ions are pumped into the ICF in the cell.
- The result is the unequal transport of positively charged ions across the membrane so that, compared to its inside, the outside of the cell becomes more positive; in other words, compared to the outside, the inside of the cell is more negative.
- Therefore, a small direct contribution to the generation of the resting membrane potential is made by the activity of the pump. The other, even more significant effect of the Na+-K+ pump is that by accumulating Na+ ions outside the cell and K+ ions inside the cell, it maintains the concentration differences in sodium and potassium.
- The predominant responsibility for generating the resting membrane potential is the passive diffusion of these ions down their concentration gradients. Sodium diffuses inward and diffuses outward with potassium.
- The pump ‘s continuous activity returns the Na+ ions to the ECF and the ICF to the K+ ions. It can therefore be said that the pump also contributes indirectly to the generation of the resting potential of the membrane.