Animations: André Malavazzi
All cells in the human body are characterized by having a net electrical charge across its membranes. We call this "membrane electrical polarization". There is a negative difference between the intracellular and the extracellular compartments, i.e., the interior of the membrane is electrically negative in relation to the exterior. This value, which is approximately -60 to -75 mV, depending on the type of cell, is called the "resting membrane potential".
How this potential appears?
Initially, we should know that there are different concentrations
of ions (Na+, Cl- and K+) inside and outside the neuron.
Under stable conditions (eletrochemical equilibrium), the Cl- and Na+ ions exist in a higher concentration outside
the cell than inside. Potassim (K+) exists in higher concentration inside than outside the cell. Furthermore, there
are some large organic anions (negative in charge), related to proteins, which exist in higher concentration inside
the cell.
How these concentration differences arise?
One of the explanations is that the neuronal membrane doesn´t let ions traverse it all at the same speed.
In other words, we say that the degree of permeability is different for each ion. Potassium has a higher permeability,
around 25 times that of sodium. Chloride has an intermediate permeability and the organic anions have an almost
zero permeability, i.e., in normal conditions they are not carried through the membrane, remaining in the cell´s
interior.
In order to understant how different permeabilities generate different concentrations,lt's repeat here the experiment
we saw in the previous section: a beaker divided into two by a biological membrane, and a salt solution of two
ions in equal concentrations on left compartment. In this example (see animation below), we will have sodium (Na+)
represented as green balls, and potassium (K+) represented as yellow balls. Concentrations on both sides are indicated
by vertical bars of the same color.
Now, instead of putting an impermeable membrane, where only
osmosis can occur, or a permeable membrane, where eventually all ions will have the same concentration of both
sides (diffusion), we put a selectively permeable membrane. This means that this membrane will have a higher permeability
to one type of ion than to another.
As ions flow to one side to the other, a electrical charge builds up gradually between the two sides of the membrane (as shown by the voltmeter needles in the figure). For the potassium ion, the right side becomes more positive than the left side and a electrical gradient appears. Since K+ is positive, it is repelled by positive charges, which it contributes by moving swiftly to the right side. Therefore, diffusion slows down and eventually an electrochemical equilibrium is reached, i.e. for every difference of chemical concentration there is an electrical potential difference that opposes it..
Thus there will be an equilibrium between electrical and chemical forces driving the movements of ions across the selectively permeable membrane and the concentrations become stable. As a result, the polarization also stops to change and becomes steady.
A German scientist named Walther Nernst expressed this phenomenon as a law which was named in his honour. It states in mathematical terms that the chemical concentrations of ions and electrical charges are in equilibrium for any given ion, and that the steady potential is proportional to the logarithm of the ratio of concentrations on each side of the membrane.
There will be a Nernst potential for each ion. For the neuron
membrane, the Nernst potential for K+ is -75 milivolts (mV). Since the neuronal membrane resting potential is around
-60 mV, we conclude that other ions must be involved besides potassium. They are Cl-, with an equilibrium potential
of -80 mV and Na+, with + 55 mV. These ions are called "the big three", because they are the most important
ones to determine membrane resting potential.
The resting potential of the membrane is a composite (a sum) of all the Nernst potentials of all ions which are
important. We name this as the Nernst-Goldman law. due to the scientist who helped to modify it. This law determines
theoretically, with great precision, the expected value for the membrane potential, as determined experimentally.
The ion with the higher speed of diffusion (in this case, K+) is the one that contributes most toward this value.
How the membrane potential is maintained?
Although Nernst law´s assures that there is an electrochemical equilibrium for each of the "big three"
ions, in reality this should be understood as a dynamic, not static, equilibrium. Ions are always switching from
one side to the other. On the long run, therefore, it would occur with neurons what always occurs with passive
semipermeable membranes, that is, concentrations in the outside and inside the cell would be equal after a time,
leading to a zero difference in membrane potencial.
Two things guarantee that the polarized state and the difference in ion concentration remain stable as long as
the cell lives.
The first is comprised by those organic anions we have mentioned above, which have a higher preponderance inside
the cells. They have a large chemical gradient from inside to the outside, but permeability is null. Therefore,
according to Nernst law, they tend to generate an electrical polarity, and contribute toward attracting positive
ions such as K+ to remain inside the cell. This special kind of equilibrium was discovered by a scientist named
Donnan.
The second is comprised by the sodium-potassium pump we have mentioned in the previous sections, which grabs all
K+ ions that go to the outside, and carry them to inside again, and grabs Na+ ions inside and carry them to the
outside. For each pumping action, it spends an energy-carrying molecule of ATP.
Now, explaining in last detail what happens with the maintenance of resting membrane potential:
1) K+ is in higher concentration inside the cell. It diffuses out of the cell at a great speed, following its chemical
gradient. Since the cell is more negative inside than outside, the electrical gradient is inverse, and this tends
to stop diffusion. Organic anions inside the cell also contribute to limit this diffusion. With time, however,
potassium would reach the same concentration inside and outside, but this is prevented by the action of the sodium-potassium
pump;
2) Na+ is in higher concentration outside the cell. It diffuses into the cell at a slower speed, following its
chemical gradient. Since the cell is more negative inside than outside, the electrical gradient is in the same
direction. By the same token, with time sodium would reach the same concentrations inside and outside, but this
is fixed up by the sodium-potassium pump;
3) Cl- is also in higher concentration outside the cell. It diffuses into the cell at a intermediate speed, following
its chemical gradient. Since the cell is more negative inside than outside, then the electrical gradient is in
the opposite direction, and limits this diffusion, reaching an equilibrium. There is no need for a Cl- pump!
Contributing to the membrane polarity, all potassium ions that come out of the cell form a fine positive layer
on the outside, just by the membrane.
Things would stay the same in perpetual equilibrium except for two things: the sudden changes of action potentials
(which inverts polarity for a brief one or two microseconds before the sodium-potassium pump arranges things nicely
up again), and the continuous input of metabolic energy to the pump.
One interesting thing is that the quantity of ions which is required to pass from one side to the other in order
to produce a potential difference is exceedingly small.
Copyright 1999 Universidade Estadual de Campinas