Ionic channels: what they are, types. and how they work in cells

Ion channels are protein complexes, located in cell membranes, which regulate vital processes such as heartbeat or the transmission of signals between neurons.

In this article we are going to explain what they consist of, what is their function and structure, what kinds of ion channels exist and their relationship with various diseases.

• Related article: "Action potential: what is it and what are its phases?"

What is an ion channel?

We understand by ion channels protein complexes filled with aqueous pores, which allow ions to pass, causing them to flow across the cell membrane. These channels are present in all cells, of which they are an essential component.

Each cell is surrounded by a membrane that separates it from the outside environment. Its lipid bilayer structure is not easily permeable to polar molecules such as amino acids or ions. Therefore, it is necessary to transport these substances in and out of the cell by means of membrane proteins such as pumps, transporters and ion channels.

the channels are made up of one or more different proteins called subunits (alpha, beta, gamma, etc.). When several of them come together, they create a circular structure in the center of which there is a hole or pore, which allows the passage of ions.

One of the particularities of these channels is their selectivity; that is, they determine that some inorganic ions pass through and not others, depending on the diameter and the distribution of its amino acids.

The opening and closing of ion channels is regulated by various factors; a specific stimulus or sensor is what determines that they fluctuate from one state to another by altering their composition.

Now let's see what functions they fulfill and what their structure is.

Functions and structure

Behind essential cellular processes, such as the secretion of neurotransmitters or the transmission of electrical signals, are the ion channels, which confer electrical and excitable capabilities to cells. And when they fail, numerous pathologies can occur (which we will talk about later).

The structure of ion channels occurs in the form of transmembrane proteins and act as a gate system to regulate the passage of ions (potassium, sodium, calcium, chlorine, etc.) through pores.

Until a few years ago it was thought that the pores and the voltage sensor were coupled through a linker or "linker" (a spiral of about 15 amino acids), which can be activated with the movement of the sensor voltage. This coupling mechanism between the two parts of the ion channel is the canonical mechanism that has always been theorized.

Recently, however, new research has uncovered another pathway that involves a segment of amino acids made up of part of the voltage sensor and part of the pore. These two segments would fit together like a zipper to trigger the opening or closing of the channel. In turn, this new mechanism could explain recent discoveries, in which some voltage-gated ion channels (some responsible for functions such as heartbeat) with just a linker.

Voltage-gated ion channels are just one of the existing channel types, but there are more: let's see what they are next.

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Types of ion channels

The mechanisms for the activation of ion channels can be of several types: by ligand, by voltage or by mechanosensitive stimuli.

1. Ligand-gated ion channels

These ion channels open in response to the binding of certain molecules and neurotransmitters. This opening mechanism is due to the interaction of a chemical substance (which can be a hormone, a peptide or a neurotransmitter) with a part of the channel called the receptor, which generates a change in free energy and modifies the conformation of the protein, opening the channel.

The recipient of the acetylcholine (a neurotransmitter involved in the transmission of signals between motor nerves and muscles) of the nicotinic type, is one of the most studied ligand-gated ion channels. It is composed of 5 subunits of 20 amino acids and is involved in basic functions such as voluntary control of movement, memory, attention, sleep, alertness, or anxiety.

2. voltage-gated ion channels

This kind of channels open in response to changes in electrical potential across the plasma membrane. Voltage-gated ion channels are involved in the transmission of electrical impulses, generating action potentials due to changes in the difference in electrical charges on both sides of the membrane.

The flow of ions takes place in two processes: by activation, a voltage-dependent process: the channel opens in response to changes in the membrane potential (difference in electrical potential on either side of the membrane); and inactivation, a process that regulates the closure of the channel.

The main function of voltage-gated ion channels is generation of action potentials and their propagation. There are several types and the main ones are:

2.1. Na+ channel

They are transmembrane proteins that allow the passage of sodium ions through the cell. Ion transport is passive and only depends on the electrochemical potential of the ion (it does not require energy in the form of an ATP molecule). In neurons, sodium channels are responsible for the rising phase of the action potential. (depolarization).

2.2. K+ channel

These ion channels constitute the most heterogeneous group of structural membrane proteins. In neurons, depolarization activates K+ channels and facilitates K+ egress from the nerve cell, leading to a repolarization of the membrane potential.

23. Ca++ channel

Calcium ions promote the fusion of the synaptic vesicle membrane (structures located in the end of the neuronal axon and responsible for secreting neurotransmitters) with the axon terminal membrane at the neuron, stimulating the release of acetylcholine into the synaptic cleft by a mechanism of exocytosis.

2.4. Cl-channel

This type of ionic channels are responsible for regulating cell excitability, transport between cells, as well as the management of PH and cell volume. Channels located in the membrane stabilize the membrane potential in excitable cells. are also responsible for the transport between cells of water and electrolytes.

3. Ion channels regulated by mechanosensitive stimuli

These ion channels open in response to mechanical actions. They can be found, for example, in Paccini's corpuscles (sensory receptors in the skin that respond to rapid vibrations and to deep mechanical pressure), which open by stretching the cell membrane through the application of tension and/or pressure.

Channelopathies: pathologies associated with these molecules

From a physiological point of view, ion channels are essential for the homeostatic balance of our body. Its dysfunction causes a whole series of diseases, known as channelopathies. These can be produced by two types of mechanisms: genetic alterations and autoimmune diseases.

Among the genetic alterations, there are mutations that occur in the coding region of the gene for an ion channel. It is common for these mutations to produce polypeptide chains that are not processed correctly and are not incorporated into the plasma membrane; or, when the subunits mate and form the channels, these are not functional.

Another frequent possibility is that, even though they are functional channels, they end up showing altered kinetics. In any case, they often lead to the gain or loss of channel function.

Also mutations can occur in the promoter region of the gene that codes for an ion channel. This can cause underexpression or overexpression of the protein, producing changes in the number of channels, which would also cause an increase or decrease in its functionality.

At present, multiple pathologies associated with ion channels in different tissues are known. At the musculoskeletal level, mutations in the voltage-gated Na+, K+, Ca++, and Cl- channels and in the acetylcholine channel lead to disorders such as hyperkalemic and hypokalemic paralysis, myotonia, malignant hyperthermia and myasthenia.

At the neuronal level, it has been proposed that alterations in voltage-gated Na+ channels, K+ and Ca++ channels by voltage, the channel activated by acetylcholine or the one activated by glycine, could explain disorders such as epilepsy, ataxia episodic migraine, familial hemiplegic migraine, Lambert-Eaton syndrome, Alzheimer's disease, Parkinson's disease, and schizophrenia.

Bibliographic references:

• J. T. Menéndez, “Pores and ionic channels regulate cell activity,” in Anales de la Real Academia Nacional de Farmacia, 2004, p. 23.
• Ana I. Fernandez-Marino, Tyler J. Harpole, Kevin Oelstrom, Lucie Delemotte, and Baron Chanda. “Gating interaction maps reveal a noncanonical electromechanical coupling mode in the Shaker K+ channel”. Nature Structural & Molecular Biology 25: 320–326, April 2018.
• g. Eisenman and J.A. Dani. Ann (1987). An introduction to molecular architecture and permeability of ion channels. Rev. Biophys. Biophys. Chemm, 16. pp. 205-226.
• Aidley, D. J. (1989) The physiology of excitable cells. Cambridge University Press.