Development of resting membrane potential

In a typical unstimulated neuron, the resting membrane potential is approximately -70 mV. The development of this potential depends on the distribution and permeability of three ions: (1) sodium (Na+); (2) potassium (K+); and (3) anions (A) (see Table 3.1 and Figure 3.1). These ions are unevenly distributed between the intracellular fluid (ICF) and the extracellular fluid (ECF) and each has a different degree of permeability across the plasma membrane. Sodium ions are found in a greater concentration in the ECF and K+ ions are found in a greater concentration in the ICF; A- refers to large anionic proteins found only within the cell. Under resting conditions, most mammalian plasma membranes are approximately 50 to 75 times more permeable to K+ ions than they are to Na+ ions. The anions are impermeable at all times. It is due to these underlying conditions that the resting membrane potential is generated and maintained.

When permeable, the movement of Na+ and K+ ions in and out of the cell depends on two factors:

• Concentration gradient

• Electrical gradient

Consider a condition in which the membrane is permeable only to potassium. Because potassium is in a greater concentration inside the cell, the K+ ions initially diffuse out of the cell down their concentration gradient. As a result, an excess of these positively charged ions would accumulate in the ECF along the external surface of the plasma membrane. Attracted to these positive charges, the impermeable A- ions would remain inside the cell along the internal surface of the plasma membrane. This outward movement of positive charges creates a negative membrane potential because the inside of the cell is now negative relative to the outside. However, as the positively charged K+ ions continue to diffuse outward, an electrical gradient begins to develop that also influences the diffusion of K+ ions.

The K+ ions that moved out of the cell down their concentration gradient have caused an excess of (+) charges to accumulate on the external surface

Table 3.1 Concentration and Permeability of Ions Responsible for Membrane Potential in a Resting Nerve Cell

Concentration (millimoles/liter)

Ion Extracellular fluid Intracellular fluid Relative permeability

EXTRACELLULAR FLUID

Plasma Membrane

PASSIVE FORCES

and associated +

3Na+

INTRACELLULAR FLUID

PASSIVE FORCES

Pump

ACTIVE FORCE

Figure 3.1 Generation of resting membrane potential. Under resting conditions, potassium (K+) is significantly more permeable than sodium (Na+) and the negatively charged intracellular anions (A-) are impermeable. Therefore, the abundant outward movement of K+ ions down their concentration gradient exerts a powerful effect, driving the membrane potential toward the equilibrium potential for potassium (-90 mV). However, the slight inward movement of Na+ ions, which would tend to drive the membrane potential toward the equilibrium potential for sodium (+60 mV), renders the membrane potential somewhat less negative. The balance of these two opposing effects results in a resting membrane potential in a typical neuron of -70 mV. The maintenance of the concentration differences for sodium and potassium is due to the continuous activity of the Na+-K+ pump.

of the membrane. Because like charges repel each other, these (+) charges would begin to repel any additional K+ ions and oppose the further movement of (+) charges outward. Instead, the positively charged K+ ions are now electrically attracted to the negatively charged A- ions remaining inside the cell. At this point, K+ ions not only diffuse outward down their concentration gradient, but also diffuse into the cell down their electrical gradient. Eventually, the subsequent force that moved K+ ions inward exactly balances the initial force that moved K+ ions outward, so there is no further net diffusion of potassium. The membrane potential at this point has reached the equilibrium potential for K+ (EK+) and is equal to -90 mV. Therefore, when the permeability of the plasma membrane to potassium is high compared to that of sodium, the membrane potential approaches -90 mV.

Next, consider a condition in which the membrane is permeable only to sodium. Because sodium is in a greater concentration outside the cell, the Na+ ions initially diffuse into the cell down their concentration gradient. As a result, an excess of these positively charged ions accumulates in the ICF along the internal surface of the plasma membrane; an excess of negative charges in the form of the impermeable extracellular anion, chloride (Cl-), remains outside the cell along the external surface of the plasma membrane. This inward movement of positive charges creates a positive membrane potential because the inside of the cell is now positive relative to the outside. However, as the positively charged Na+ ions continue to diffuse inward, once again an electrical gradient develops.

The (+) charges that have accumulated in the ICF begin to repel any additional Na+ ions and oppose the further movement of (+) charges inward. Instead, the positively charged Na+ ions are now attracted to the negatively charged Cl- ions remaining outside the cell. Eventually, the initial force moving Na+ ions inward down their concentration gradient is exactly balanced by the subsequent force moving Na+ ions outward down their electrical gradient, so there is no further net diffusion of sodium. The membrane potential at this point has reached the equilibrium potential for Na+ (ENa+) and is equal to +60 mV. Therefore, when the permeability of the plasma membrane to sodium is high compared to that of potassium, the membrane potential approaches +60 mV.

At any given time, the membrane potential is closer to the equilibrium potential of the more permeable ion. Under normal resting conditions, Na+ ions and K+ ions are permeable; however, potassium is significantly (50 to 75 times) more permeable than sodium. Therefore, a large number of K+ ions diffuse outward and a very small number of Na+ ions diffuse inward down their concentration gradients. As a result, the comparatively copious outward movement of K+ ions exerts a powerful influence on the value of the resting membrane potential, driving it toward its equilibrium potential of -90 mV. However, the slight inward movement of Na+ ions that would tend to drive the membrane potential toward its equilibrium potential of +60 mV renders the membrane potential slightly less negative. The balance of these two opposing effects results in a typical neuron resting membrane potential of -70 mV (see Figure 3.1).

The Na+-K+ pump also plays a vital role in this process. For each molecule of ATP expended, three Na+ ions are pumped out of the cell into the ECF and two K+ ions are pumped into the cell into the ICF. The result is the unequal transport of positively charged ions across the membrane such that the outside of the cell becomes more positive compared to its inside; in other words, the inside of the cell is more negative compared to the outside. Therefore, the activity of the pump makes a small direct contribution to generation of the resting membrane potential.

The other, even more important effect of the Na+-K+ pump is that it maintains the concentration differences for sodium and potassium by accumulating Na+ ions outside the cell and K+ ions inside the cell. As previously discussed, the passive diffusion of these ions down their concentration gradients is predominantly responsible for generating the resting membrane potential. Sodium diffuses inward and potassium diffuses outward. The continuous activity of the pump returns the Na+ ions to the ECF and the K+ ions to the ICF. Therefore, it can be said that the pump also makes an indirect contribution to generation of the resting membrane potential.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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