Transmembrane protein series two: Ion Channels

1. Ion Channel Definition

Ion channels, commonly called channel proteins, are pore-forming membrane proteins that allow ions to pass through channel pores. Ion channels are the basic excitatory unit in the cell membrane of many tissues such as nerves, muscles, and glands. Living cells must exchange substances with the surrounding environment continuously to carry out metabolic activities, and ion channels on the cell membrane are an important way of such material exchange.

Some stimuli bind to and interact with the channel proteins on the cell membrane, changing the conformation of ion channels. Conformational alteration of ion channels regulates the opening and closing of ion channels, modulating the ability of corresponding substances to enter and exit cells, thereby regulating various key physiological processes of the living system. Sometimes ion channel gating is controlled by the membrane potential. Almost all cellular processes rely on ion channels.

2. Characteristics of Ion Channels

Ion channels have two common characteristics: ion selectivity and gate control. Ion selectivity includes ion size selectivity and charge selectivity of the channel. Under certain conditions, an ion can only be diffused across the membrane through its corresponding channel. Another characteristic is the gating characteristic of ion channels. Ion channels generally have corresponding gates. The opening and closing process of channel gates is called gating.

Ion channels can be shown in three states:

(1) Activation

Under the action of external factors, the ion channel allows one or some ions to pass through the membrane along the concentration difference and potential difference, which is equivalent to the opening of the channel.

(2) Inactivation

Channel inactivation is not the same as channel closure.

(3) Closed State

The channel closure is the state of the channel at rest. At this time, if the channel is stimulated by the appropriate stimulus, it can enter the activated state.

3. Classification of Ion Channels

According to different gating mechanisms, ion channels can be divided into three categories:voltage-gated ion channels, ligand-gated ion channels, and mechanically gated ion channels.

3.1 Voltage-gated Ion Channels

Voltage-gated ion channels are also known as voltage-dependent or voltage-sensitive ion channels. The voltage-gated ion channels consist of sodium, potassium, and calcium plasma channels, which are usually enclosed by four transmembrane segments of the same subunit into pores. Pores have some charged groups (potential sensors) that control the gate.

When the transmembrane potential changes, the electric sensor generates displacement under the action of the electric field force in response to the change of the membrane potential, resulting in the opening or closing of the gate. The aperture and charge distribution of the orifice forms an ion selector, but are not absolutely opaque to other ions.

3.2 Ligand-gated Ion Channels

Ligand-gated ion channels, also known as chemically gated ion channels, are channels that are activated or repressed by transmitters, hormones, or other chemicals inside and outside the cell.

3.3 Mechanically Gated Ion Channels

Mechanically gated ion channels are also known as mechanically sensitive ion channels. The opening probability of mechanically gated ion channels varies significantly with the mechanical stress on the channel proteins.

In addition, there are organelle ion channels, such as voltage-dependent anion channels widely distributed in the outer membrane of mammalian mitochondria and receptor channels located on the membranes of the sarcoplasmic reticulum or endoplasmic reticulum.

4. Ion Channel Function

As the basic excitatory unit in the cell membrane of many tissues such as nerves, muscles, and glands, ion channels have many important physiological functions.

The basic function of ion channels is the substance absorption.

Signal transmission. Certain ions (Ca²⁺, K⁺, etc.) in the cytoplasm rapidly increase in concentration to form signal stimulation, further affecting downstream signaling pathways. Ion channels are the primary channel for adjusting ion concentration.

The increase in intracellular calcium concentration triggers a series of physiological effects such as muscle contraction, cell excitation, glandular secretion, Ca2²⁺-dependent ion channel opening and closing, protein kinase activation, and gene expression regulation.

Osmotic pressure regulation. In excitatory cells such as nerves and muscles, Na⁺ and Ca²⁺ channels mainly regulate depolarization, and K⁺ channels mainly regulate repolarization and maintain resting potential, thus determining the excitability, impermeability, and conductivity of cells.

Electrical impulse formation. The various sensory mechanisms of animals, such as vision, taste, smell, and temperature perception, are related to changes in potential caused by ion channels.

Regulating vasomotor activities of vascular smooth muscle. K⁺, Ca²⁺, Cl^- channels, and some non-selective cation channels are involved in these activities.

Involvement in synaptic transmission. K⁺, Na⁺, Ca²⁺, Cl^- channels, and some non-selective cation channels participate in these activities.

Maintaining the normal volume of cells. In a hypertonic environment, the activation of ion channels and transport systems allows Na⁺, Cl^-, organic solution, and water to enter cells and increase cell volume. In the hypotonic environment, Na⁺, Cl^-, organic solution, and water flow out of the cells and decrease the cell volume.

5. Ion Channel List

Information in this table is sourced from: https://www.genenames.org/data/genegroup/#!/group/177

6. Ion Channel Proteins for research use

Abnormal ion channels have been linked to a range of diseases, including epilepsy, arrhythmia, schizophrenia, and diabetes. Ion channels have a certain relationship with tumors. Ion channels also play a conservative role in development.

Ion channels and their correlation with nerves, cardiovascular, immune diseases, and cancer make ion channels an important target for drug design. Different target drugs can be designed according to different types of channels.

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