Communicators 1: the primary signal

In the course of evolution, in parallel with their increased size and complexity, biological organisms have developed a highly refined network of communication within the cell. They have also developed more complex communications between different cells that are near and far from the source of the primary signal.

The construction of an information exchange system was necessary to be able to have precise control over the various parts of the organism. In addition, the ability to control the relationship with the surrounding environment was equally important. The possibility to monitor all the spatial/temporal information coming from outside the organism was instrumental to develop a diffuse system to acquire, elaborate and respond to a vast variety of external stimuli.

The ways in which communication takes place between the inside and the outside of the organism or between the various parts of the organism have evolved with its size and with the specialization of its different regions.

In general, the transfer of information within cells and between cells is essentially chemical, electrical or both, in appropriate combinations. However, chemical and electrical transmission are not interchangeable, as they have their own particular characteristics with respect to the different ways communication takes place in the biological sphere.

If, for example, the speed of information transfer is essential, the electrical mode is the most suitable, operating with times in the order of micro- and milliseconds. If, on the other hand, the time span of the message covers minutes, hours or days, it is clear that the potential of chemical modes of transmission is unlimited. The latter considerations do not exclude a slow electrical signal and a fast chemical information transfer These ideas will be explored in more detail in the following chapters.

In the communication system between cells, the primary electrical signal is generally the event known as the action potential, an electrochemical phenomenon involving charges carried by ions, which essentially affects the difference of potential across the membranes. The action potential is the basis for the transfer of information both in and out of the biological organism and is mainly characterized by the fact that it is generated in a few milliseconds; there are a few examples of long-lasting action potentials (seconds and also minutes).

The action potential is a passive phenomenon, in that its generation does not require the simultaneous production of energy, but instead exploits the potential energy needed to maintain the potential difference across the membranes of excitable cells. These cells have resting membrane potential values approximately between -60 and -90 mV, a potential close to the equilibrium potential of the potassium ion.

The potential difference is maintained by the presence of constraints, namely a very low and extremely selective membrane electrical permeability. These constraints, in the presence of an appropriate stimulus, are momentarily removed, allowing the biological system to move spontaneously and rapidly towards a stable equilibrium. The complete cycle includes the ability to re-establish the original conditions at a high level of potential energy.

In practice, the mechanism consists of a depolarization of the membrane lasting one to two milliseconds from the resting potential to a positive value of around +30 to +40 mV, which is close to the equilibrium potential of the sodium ion; the depolarization activates a mechanism that, at the end of the upstroke, is able to return the membrane potential to its initial value.

The result of this process is the generation of a transient signal of approximately 100 mV in amplitude, which varies in duration, depending on the type of cell, from a few milliseconds to several minutes.

Four characteristics of the action potential should be emphasized: transient occurrence, low energy consumption, defined amplitude, and the digital nature of the signal.

The transient occurrence makes the action potential a communication system that does not produce permanent changes in the physiology of the cell that generates the signal. Quantification of inward and outward ionic flows demonstrated a negligible amount of ions crossing the membrane during the action potential (10⁵-10⁶ ions), which is several orders of magnitude less than the ion content in the intracellular and extracellular fluids (10²² ions).

The consumption of energy is practically zero, as the single action potential wave generated uses a very small part of the potential energy accumulated in the form of electrochemical potential. A dissected sciatic nerve placed in an experimental chamber without nutrients is able to produce action potentials for several hours without apparent signs of fatigue. As mentioned above, the amplitude of the signal of about 100 mV fluctuates between the potassium and sodium equilibrium potentials.

It is important to notice that, once triggered, the action potential wave cannot be modulated in amplitude. Finally, being an all-or-none event, the action potential can be defined as a digital signal. The code used by the excitable cells to communicate is the frequency of action potentials (firing frequency).

What has just been described represents a generic wave of excitation of nerve cells (Figure 5.1): it will be seen that its duration can vary, depending on the type of neuronal cell, from one to tens of milliseconds, while its amplitude strictly varies between the equilibrium potential of potassium and that of sodium and is therefore immutable regardless of cell type.

Due to its digital nature, the single action potential, which goes from a value = 0, close to the potassium equilibrium potential, to a value = 1, close to the sodium equilibrium potential, does not have functional significance. It is not uncommon for nerve cells to have irregular spontaneous activity in which single action potentials are randomly produced that do not, in fact, constitute a message for other cells.

While a digital signal cannot be modulated in amplitude, the signal for communication between different cells can be modulated in frequency with the generation of spike trains of action potentials or neuronal firings. Neuronal firing consists of a large number of individual events that are generated at regular time intervals and in such a way that different frequencies can encode different functions.

For the sake of completeness regarding the communication process between cells, it is necessary to point out that the phenomenon of excitability does not only apply to nerve cells, but also to muscle cells, oocytes and certain glandular cells, all of which are capable of responding to particular stimuli with a sudden change of the membrane potential.

In these cases, the generation of an action potential is closely linked to a specific function. In the cardiac action potential, at the ventricular level, the action potential lasts several hundred milliseconds. The depolarization is maintained by additional membrane calcium channels.

In order to study the principles of cellular excitability, we will consider a model of a cell whose characteristics are as similar as possible to those of a neuron, the predominant cell type involved in cellular excitability in the mammalian nervous system. Action potential generation in the neuron can be used as an illustration of the basic mechanism of cell excitability.

Specific aspects of excitability in different tissues and specialized cells can be evaluated on the basis of the neuronal action potential. For example, during fertilization, the oocyte produces an action potential lasting 30-40 minutes to prevent polyspermy. This action potential is basically equal to a nervous action potential lasting a few milliseconds, with the addition of a calcium conductance able to maintain a long-lasting depolarization.