Ion channels and gradients

Structure

Ion channels are proteins that span across the cell membrane and are firmly inserted into the phospholipid bilayer (transmembrane proteins). They are made up from transmembrane subunits that assemble to form a pore and accessory structures. The number of these subunits varies across different subfamilies of ion channels.

Function

Ion channels fulfill three main functions:

1. Facilitation of ion transport: Due to its structure and properties, the phospholipid bilayer actively inhibits the passage of charged molecules across the cell membrane. Ion channels enable ions to pass through them passively, without energy consumption. When the pore is open, ions can diffuse down their respective electrochemical gradients, reaching an astonishing rate of 10 million ions per second.
2. Selectivity: The majority of the ion channels are highly selective, allowing only specific ions to traverse through them.
3. Activation in response to stimuli: Due to their unique protein structure, ion channels maintain a closed state, preventing ions from passing through. However, in response to various stimuli, which can be of electrical, chemical or mechanical nature, the structure of the channel can change, leading to the opening of the pore, allowing ions to pass. An exception to this pattern of activation/deactivation are the leakage ion channels that are constantly activated and thus remain in an open state.

Ion selectivity

The movement of ions through their respective channels occurs without energy consumption. It is solely driven by the electrochemical gradient, which dictates the net flow of ions across the cell membrane. A fundamental question, however, is how ion channels achieve selectivity, allowing only specific ions to pass through. The prevailing theory on the mechanisms underlying this selectivity points to a combination of factors which include ion size, electrical charge and interaction with the channel's structure:

1. Role of ion size and electrical charge: Ions vary in size and electrical charge, attracting different numbers of water molecules around them (hydration shell). For instance, Na⁺ is smaller than K⁺ and carries a greater electrical charge due to its reduced size. Consequently, each Na⁺ ion is surrounded by more water molecules, forming a larger hydration shell compared to K⁺.
2. Pore size limitation: The ion channel pore is too small to accommodate ions surrounded by a hydration shell of water molecules. Therefore, ions must discard these water molecules to pass through the pore, a process demanding a substantial amount of energy.
3. Electrical charge of the pore: The lining of the pore is charged, which allows for a selective passage of anions or cations, respectively.

In the case of Na⁺ channels, specific regions inside the pore contain amino acids, such as aspartic and glutamic acid, carrying a negative electric charge sufficient to attract Na⁺ ions. This attraction provides the ions with the necessary energy to discard some of their surrounding water molecules, reducing their size to a point where they can effectively diffuse down their electrochemical gradient and pass through the channel's pore. Given its larger diameter, K⁺ cannot approach these negatively charged regions of the pore close enough to benefit from this energy-boosting mechanism, making it ineffective for K⁺ to traverse Na⁺ channels.

Conversely, the pores of K⁺ channels have regions with carbonyl and hydroxyl oxygen atoms featuring a weaker electrical field. In these regions, K⁺ ions can interact and release the surrounding water molecules, enabling K⁺ ions to pass through the channel. However, the energy present in these regions is insufficient for Na⁺ ions to release their water molecules and traverse the channel.

Ion channel gating

Another vital aspect of ion channels involves the dynamic state of their pores. They possess the ability to modify their protein structure, either opening or closing the ion passage. The transformation from one structural state to another is termed gating.

There are three fundamental models which characterize the structural changes ion channels undergo following gating. It is important to note that some ion channels may employ a combination of these models to establish their distinct stable protein configurations:

1. In the first model, the structural transformation occurs within a specific region of the channel's lumen. During gating, only the structure within this specific territory undergoes changes to open or close the lumen.
2. In the second model, the transition from one functional structure to another involves changes across the entire lumen rather than in a specific region.
3. The third model involves a distinct mechanism where no changes take place within the lumen itself. Instead, a particle binds to the lumen's orifice, effectively sealing the ion channel pore.

The structural changes ion channels undergo are linked to specific functional states that can be categorized as follows:

• Activated: In this state, ions can pass through the channel.
• Deactivated: In the deactivated state, no ions pass through the channel. However, with the introduction of specific stimuli, it can be prompted to open and become activated.
• Permanently deactivated or inactivated: When ion channels are in the inactivated state, they do not permit ion passage, but they can also not be activated, even when exposed to appropriate stimuli.

Types of ion channels

The functional states of ion channels are regulated by various stimuli. These can trigger the structural protein changes in each ion channel, providing the energy required to facilitate the structural transition of the channel itself. Ion channels can be categorized into various types based on their activation/deactivation pattern and the specific stimuli they respond to.