ION CHANNELS: STRUCTURE, FUNCTIONS, TYPES - BIOLOGY - 2025

The ion channels are a hollow membrane structures that form channels or pores traversing the thickness of the membrane and communicating the exterior of the cell with its cytosol and vice versa; some may have a gate system that regulates their opening.

These channels are filled with water and control the passage of specific ions from one side of the membrane to the other. They are made up of proteins typical of cell membranes that form cylindrical tube-shaped structures that cross them in width.

Open and closed formation of an ion channel (Source: Efazzari via Wikimedia Commons)

The transport mechanisms across these membranes can be broadly classified into passive or active transport. Passives are those that allow the passage of substances in favor of their concentration gradients, while active ones require the consumption of energy, since they move substances against their concentration gradients.

Ion channels constitute a passive transport mechanism that can be classified according to their specificity, that is, according to the type of ion that they allow to pass, or according to the way in which they open or close.

The main function of these membrane transport systems is to allow the regulated passage of substances into or out of cells and thus maintain intracellular concentrations of ions and other substances.

The presence of cell membranes and ion channels is essential for the maintenance of concentration differences between the intracellular and extracellular media, which is relevant from many points of view.

Ion channels, especially ligand-dependent ones, are very important in pharmacology and medicine, since many drugs can mimic the functions of natural ligands and thus bind to the channel, opening or closing it, as the case may be.

Other drugs are able to block the binding site and thus prevent the action of the natural ligand.

Structure

The structure of ion channels is made up of specific transmembrane proteins that have a tubular shape and leave a pore or hole that allows communication between the inside and outside of the cell or between intracellular compartments (organelles).

Each ion channel involves a specific structural membrane protein, and more than 100 genes have been described that encode specific ion channels.

For the sodium channel, for example, 10 genes called SCNs have been described that encode different proteins distributed in different tissues with particular functions and structures.

Likewise, a considerable number of genes have been described that encode different proteins that make up potassium channels that belong to different families and possess different activation, opening and inactivation mechanisms.

Protein structure of an ion channel

Typically, a functional ion channel associated with a membrane is composed of the assembly of 4 to 6 similar polypeptide subunits (homo oligomers) or different (hetero oligomers) that form a central pore between them.

Diagram of the membrane subunits of an ion channel (Source: Efazzari via Wikimedia Commons)

Each subunit varies according to the characteristics and properties of the channel, since many are specific for certain ions and have different opening and closing mechanisms.

Some channels are made up of a single polypeptide chain organized in repeating patterns that go through several times the thickness of the membrane and function as the equivalent of a protein subunit.

In addition to these subunits, which are known in the literature as α subunits, some ion channels also have one or more auxiliary subunits (ß or γ) that regulate their opening and closing.

The specificity of each channel is related to the diameter of the pore formed by the transmembrane proteins and the side chains (─R) of the amino acids that make them up.

In this way, there are channels that only let sodium, potassium, calcium ions pass through, and so on, since the side chains function as a "sieve".

Additional structural features

Another important feature of many channels is the gates. Channels with these properties can open or close against local changes that occur in the membrane microenvironment that surrounds the channel.

Depending on the type of channel, these changes can be mechanical, thermal (changes in temperature), electrical (changes in voltage) or chemical (binding of a ligand).

However, in the so-called passive ion channels, which are those that remain open and allow the specific passage of certain ions, these structures do not have gates or are sensitive to ligands or other types of stimuli.

In other ion channels, which are sensitive to the presence or binding of ligands, there is a binding site for ligand either on the extracellular side or towards the cell cytosol and in these cases the pores or channels have a gate that can be opened or closed according to the state of its ligand.

Second messenger mechanism for opening or closing channels

In the case of having a ligand site in the intracellular portion, these channels usually have second messengers as ligands. An example of ion channels that are opened or closed by second messenger mechanisms is that of olfactory receptors:

Scent molecules bind to their receptors on the extracellular side. These receptors, in turn, are attached to an activated G protein that, in turn, activates the protein adenyl cyclase that forms cAMP, which is a second messenger.

The cAMP binds to an intracellular binding site of some calcium channels, which results in its opening and the entry of calcium into the cell.

As if it were a domino effect, calcium binds to a ligand site of another chlorine channel, which generates its opening and the exit of this ion, causing the depolarization of the olfactory cell.

It is important to highlight that the changes generated by the ligands or the stimuli that affect the ion channels correspond to conformational changes of the proteins that constitute the structure of the channel.

In other words, the conformational changes that can move a gate and close or open a channel are nothing more than the approaching or distancing of the protein subunits that compose it.

Other activation and inactivation mechanisms

Some channels, especially voltage-dependent channels, can enter a refractory state during which the same voltage change that activated them now no longer activates them.

For example, in voltage-gated calcium channels, the voltage change opens the channel and calcium enters and, once inside the cell, the same ion binds to a calcium channel binding site and the calcium channel closes..

Another form of reversible inactivation of the calcium channel that explains its refractoriness after activation is dephosphorylation of the channel due to increased internal calcium concentration.

That is, a calcium channel can be irreversibly inactivated due to the presence of pathologically high concentrations of the ion, which mediate the recruitment of cleavage enzymes from other calcium-activated proteins.

Ligand-gated channels can enter a refractory state when exposed to their ligand for a long time, this mechanism being called desensitization.

Drugs, poisons and toxins can affect the regulation of ion channels, closing or keeping them open or, in some cases, occupying the site of the ligand and thus interfering with its function.

Features

Ion channels have a multiplicity of functions, direct or indirect.

- They are responsible for regulating the flow of ions through the plasma and organellar membranes of all cells.

- They allow the existence of a control over the intracellular concentrations of the different ions.

- In neurons and muscle cells, ion channels control the variations in membrane potential that occur during action potentials and during effector cell postsynaptic potentials.

- The calcium channels that generate net flows of calcium into the intracellular space are responsible for the activation of numerous enzymes and proteins that participate in many metabolic processes.

- Likewise, the increase in calcium due to an increase in its transport initiates the release mechanism of neurotransmitters to the synaptic space of neurons.

- Therefore, the function of ion channels is also related to the mechanisms of cellular communication.

Generalities of transport across the membrane

As stated above, membrane transport mechanisms can be active or passive depending on whether or not they consume energy from the cell where they are located. Passive mechanisms are classified into simple diffusion and facilitated diffusion.

Simple diffusion

Simple diffusion allows the passage through the phospholipid structure of the membrane of fat-soluble molecules of small size, with apolar characteristics and without charge.

Thus, for example, gases such as oxygen (O2) and carbon dioxide (CO2), ethanol and urea, to name a few, pass through their concentration gradient.

Facilitated dissemination

Facilitated diffusion is one that is facilitated by proteins and there are two types of this passive transport mechanism: ion channels and transport proteins or transporter proteins.

Ion channels are the mechanism most used by cells for the transport of ions that cannot pass by simple diffusion, either because they have an electrical charge and the phospholipids of the membrane repel them, due to their size and polarity or any other characteristic.

Diffusion facilitated by carrier proteins is used for the transport of larger substances with or without charge, such as glucose and other sugars.

Active membrane transport is that which occurs against the concentration gradient of the solute being transported and requires the consumption of energy in the form of ATP. Among the transporters of this type are pumps and vesicular transport.

As an example of the pumps is the sodium / potassium pump, which removes three sodium and introduces two potassium. There are also the calcium pumps.

Examples of vesicular transport are endocytosis, exocytosis, pinocytosis, and phagocytosis; all these active transport mechanisms.

Types of ion channels

From this point on, reference will be made to the ion channels that allow the passage of ions through a membrane in favor of their concentration gradients, that is, they are passive transport channels.

Generally, each of these channels is specific for a single ion, with the exception of a few channels that allow the transport of ion pairs.

Structural diagram of an ion channel (Source: Outslider (Paweł Tokarz) at pl.wikipedia via Wikimedia Commons)

One way to classify ion channels is by grouping them according to the mechanism responsible for their opening. Thus, passive channels, voltage-regulated (voltage-dependent) channels, ligand-regulated channels, and mechanical stimulus-regulated channels have been described.

- Passive channels: they are channels that are permanently open and do not respond to any type of stimulus; these are specific for certain ions.

- Voltage-dependent channels: these can open or close (depending on the channel) in the face of changes in the membrane voltage. They are very important for cell signaling, especially in the central nervous system of mammals.

- Ligand-dependent channels: also called ligand- gated or ligand-regulated channels, they are widely distributed in the different human body cells, but in the nervous system they constitute those ionic channels activated by neurotransmitters and are essential for synaptic transmission and intercellular signaling.

Example of ligand-dependent ion channels activated by neurotransmitters are sodium / potassium channels activated by glutamate.

The activation of cholinergic receptors, in this case the binding of acetylcholine to the postsynaptic membrane (channel ligand), opens ligand-dependent sodium channels and allows the entry of this ion following its concentration gradient.

- Channels regulated by mechanical stimuli: these are channels that can be activated by distension or pressure. These mechanical forces are transmitted to the canal through the cytoskeleton and the canal opens.

References

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