Electrical signalling in neurons

Neurons are excitable cells, meaning that they respond to stimulation and can generate nerve impulses. These travel along axons at speeds of up to 120 metres per second, which permits rapid, long-distance communication between different parts of the nervous system. This chapter will examine the electrical properties of neurons and the cellular basis of excitability and axonal conduction.

The neuron at rest

There is a small difference in electrical potential across the plasma membrane of all living cells, the inside usually being slightly negative compared to the outside. This potential difference is referred to as the membrane potential of the cell. It is due to a slight excess of negative charge on the inner face of the plasma membrane and is measured in millivolts (mV). The resting membrane potential can be recorded with an intracellular microelectrode and its value is typically around –70 mV in nerve cells (Fig. 6.1).

Fig. 6.1 The resting membrane potential.
The potential difference across the cell membrane of a typical neuron is around –70 millivolts (negative on the inside).

The neuronal membrane is therefore said to be polarized at rest. An increase in polarization (so that the interior of the cell becomes even more negative) is referred to as hyperpolarization. Loss of normal polarity (so that the membrane potential moves closer to zero) is termed depolarization. It is important to understand that the uneven charge distribution responsible for the membrane potential is restricted to the immediate vicinity of the cell membrane. This means that there is a very small excess of negative charge on the inner face of the membrane, balanced by an equal amount of positive charge on the outer face. By contrast, the comparatively vast volumes of intracellular and extracellular fluid are electrically neutral.

Origin of the resting membrane potential

The resting membrane potential of –70 mV is mainly due to the efflux of positively charged potassium ions (K⁺). These diffuse out of the cell via leak channels, leaving the inner face of the membrane slightly electronegative. The driving force for potassium efflux is passive diffusion, since the concentration of potassium inside the cell is 30 to 40 times higher than that of the extracellular fluid. Permeability to other ions is much less at rest, so the resting membrane potential is mainly determined by the potassium gradient. The sodium gradient is more important for changes that occur when the cell is stimulated (discussed below).

The transmembrane gradients for sodium and potassium are maintained in the long term by the sodium-potassium exchange pump (‘sodium pump’) which works continuously in the background (Fig. 6.2). The sodium pump is a membrane-bound protein that hydrolyses adenosine triphosphate (ATP) and uses the energy released to move ions across the plasma membrane against their concentration gradients. In each cycle the sodium-potassium pump (or Na⁺/K⁺-ATPase) transfers three sodium ions out of the cell and moves two potassium ions into the cell, consuming a single molecule of ATP in the process. In this way, the intracellular potassium concentration is maintained at approximately 140 mM compared to the extracellular concentration of around 3–5.5 mM, representing a potassium gradient of around 35 : 1 (higher on the inside). In contrast, the sodium ion concentration is around 12 mM on the inside and 140 mM on the outside, which equates to a 12 : 1 gradient for sodium ions (higher on the outside).

Fig. 6.2 The sodium-potassium exchange pump.
Na⁺/K⁺-ATPase (‘the sodium pump’) is responsible for maintaining the intracellular and extracellular sodium and potassium gradients in the long term.

The sodium pump accounts for two thirds of the basal energy expenditure in nerve cells. It also contributes to the excess of negative charge on the inner face of the plasma membrane since it expels three positively charged ions in each cycle but only imports two. It is therefore described as electrogenic and the resting membrane potential is 3–5 mV more negative than predicted from passive ion flow.

Key Points

The neuronal membrane is polarized, with a resting membrane potential of –70 mV (negative on the inside) due to a slight excess of negative charge on the inner face of the membrane.

An increase in the membrane potential (so that it becomes more negative) is called hyperpolarization. Movement of the membrane potential closer to zero is depolarization.

The resting membrane potential is mainly due to efflux of potassium (K⁺) ions via leak channels. This depends on the steep concentration gradient for potassium (35× higher on the inside).

Sodium is more concentrated in the extracellular fluid and the sodium gradient (12× higher on the outside) is more important for depolarizing the cell during a nerve impulse.

The sodium and potassium gradients are maintained in the long term by the sodium-potassium pump, which is responsible for two thirds of the basal energy expenditure in the brain.

Ionic basis of the resting membrane potential

Consider the hypothetical membrane-bound cell depicted in Figure 6.3A. It contains a concentrated solution of potassium salt and is immersed in saline (a solution of sodium chloride). It is important to emphasize that although only potassium (K⁺) is illustrated in the figure, the intracellular and extracellular fluids contain many different positive and negative ions and are electrically neutral overall.

Now suppose that the cell membrane is exclusively permeable to potassium. Since the intracellular concentration is much higher, potassium will passively diffuse out of the cell down its steep concentration gradient (Fig. 6.3B). A slight excess of negative charge will therefore build up on the inner face of the membrane, since each potassium ion that leaves the cell carries a single positive charge. However, this generates a growing electrical field that acts in the opposite direction to the concentration gradient and tends to attract potassium back inside the cell. The net efflux of potassium ions is therefore gradually reduced as the opposing electrical field builds up.

Ultimately the rate of potassium efflux (down its concentration gradient) is exactly counterbalanced by potassium influx (down the electrical gradient) and there is no net movement of potassium ions into or out of the cell (Fig. 6.3C). At this equilibrium point the membrane potential is stable and will be slightly more negative on the inside. The potential difference across the membrane at this point is the equilibrium potential for potassium and is around –90 mV. It should be emphasized that this process is very rapid (the equilibrium point is reached almost instantaneously).

The absolute number of ions moving across the cell membrane to establish the equilibrium potential is a few tens of millions, which is a negligible fraction of the total number of potassium ions inside the cell. The intracellular potassium concentration is therefore unchanged.

Figure 6.6A shows the effect of opening additional chloride channels in a membrane that is initially polarized to a value of –60 mV. In this case the membrane is hyperpolarized (from –60 mV to –65 mV). In Figure 6.6B the cell membrane is already at the equilibrium potential for chloride (–65 mV) when the additional chloride channels are opened, so there is no change in membrane voltage (no net ion flux). In Figure 6.6C, the cell membrane starts at a value of –70 mV, which is more negative than the chloride equilibrium potential. Therefore, as the chloride conductance is increased the membrane is depolarized (from –70 mV, towards –65 mV).

The point at which the direction of net current flow reverses is called the reversal potential and is the same as the equilibrium potential. The rate of net current flow for a particular ion is proportional to the difference between the membrane potential and the equilibrium potential for that ion. This is referred to as the driving force. If the membrane potential is the same as the reversal potential, then the driving force is zero.

Key Points