4.2: Ion channels

The cell membrane that separates the inside of the cell from the outside is a very effective boundary. It is described as being selectively permeable, which means that some molecules are able to travel across the membrane easily, other molecules have an intermediate ability to cross, and other molecules are completely incapable of passing. Generally, gases and molecules of water are able to pass through the cell membrane easily. Large molecules like glucose, and charged molecules like ions or amino acids, are unable to pass across the membrane.

Most cells of the body, including neurons, have specialized transmembrane proteins embedded in the cell membrane. These transmembrane proteins are huge protein complexes that span the entirety of the membrane, with an outer side and an inner side. In the middle of the protein is a pore, which is essentially a “tunnel” that allows molecules and ions to pass across the cell membrane. These proteins are called ion channels. These channels are passive since they do not use any cellular energy to move ions. Rather, they simply provide easy passage for ions. It may be useful to think of an ion channel as a “cellular door.”

One important feature of ion channels is their ability to distinguish ions based on their chemical properties. For example, some channels are selective for Na+, while preventing the passage of all other ions. Each ion channel has special molecular characteristics that allow certain types of ions to pass through the pore while excluding other ions. Some features that allow for distinction between ions include:

Figure 4.1 Selective permeability of molecules across the cell membrane.

Figure 4.2 Ion channels (purple) are transmembrane proteins that can be open, allowing charged ions to cross the cell membrane through a molecular “tunnel” called the pore.

1. Pore size. The molecular shape of an ion channel can exclude larger diameter ions if it is small enough, restricting the ability for the large ion to enter the pore – in the same way that a ping pong ball cannot pass through a narrow diameter of a straw.

2. Electrical charge. Ion channels can also prevent certain ions from passing through based on the electrical charge. The inside of the pore is lined with charged amino acids, and their charge allows only certain types of ions to pass. For example, sodium channels have several negatively-charged glutamate residues inside the pore. Because of this, negatively-charged ions like chloride will be repelled by the negative charges, but the positively-charged sodium ions will be attracted to the inside.

Figure 4.3 Ions dissolved in water are surrounded by a shell of water molecules. The potassium ion is larger, and the water molecules are farther apart, making the attraction weaker than in the sodium ion.

3. Hydration shell. Selectivity based on charge and small size is a simple task, but how can it be possible for an ion channel to allow larger ions to pass while excluding smaller ions? This is possible because it is energetically favorable to allow an ion that has been stabilized sufficiently by the properties of the amino acid residues lining the pore.

This process is related to the observation that a shell of water molecules surrounds each charged ion in solution. To pass through the pore, water molecules must be separated from the ion. The potassium ion has diffuse hydration shell, and so it is easier to separate water from a potassium ion compared to a sodium ion. The passage of potassium becomes more energetically favorable compared to passing a sodium ion, causing these pores to be selective.

Like doors, different types of ion channels open and close under different conditions. We can categorize ion channels into four major classes based on their opening and closing conditions.

1. Leak channels are persistently open. You can think of these leak channels as revolving doors that are never locked. Neurons usually have several leak channels, such as a leak channel for potassium (K+) and a leak channel for chloride (Cl-) ions. These two ions are at equilibrium, flowing back and forth across the cell membrane, and they help contribute to the properties of the neuron at rest.

3. Ligand-gated ion channels open in response to binding certain molecules (ligands), such as neurotransmitters. These types of ion channels are also called ionotropic receptors, and these will be described in much more depth in chapter 5.

4. The fourth class of ion channels is a catch-all category that includes a wide variety of channels that are used by the sensory systems. They open and close in response to unique stimuli depending on what they are able to sense. For example, some open and close depending when they are moved physically, such as a distortion or stretch. We have these in our ears (hair cells, chapter 8.1), in our skin (Pacinian corpuscles, chapter 8.3) and in our muscles (Golgi tendon organ, chapter 10). Photoreceptors in our eyes have ion channels that close in response to being hit by photons of light, and this activity is necessary for us to be able to see in both brightly and dimly lit environments.