Channels

Channels are the simplest membrane transport proteins. The simplest channel would be a protein that formed a hole in the membrane, allowing molecules to pass in or out of the cell all the time. Such a channel would quickly kill the cell because it would result in an influx of calcium ions into the cell, which would trigger cell death. Even if calcium ions were excluded the loss of key metabolites and the loss of the gradients of ions that maintain the membrane potential would result in cell death. As a consequence, channels are generally quite specialized in their function.

There are three main types of channels that can be found in the cell membrane: ion channels, water channels (aquaporins) and gap junction channels. Ion channels and water channels are found in the cell membranes of almost all cells. Gap junction channels are more specialized and only found in cells that are electrically and metabolically coupled to neighboring cells.

Ion Channels

The function of ion channel proteins is captured almost perfectly by their name, they are channels through which ions can pass across the membrane. Ion channels are integral membrane proteins with a central pore that can shield the charged ions from the hydrophobic lipid bilayer as the ions cross the cell membrane.

One key property of different ion channels is ion selectivity. Most channels only allow a subset of the ions commonly found in biological solutions to pass through the channel (Figure 1). They will usually only allow either cations or anions to pass but not both. Many channels are even more selective and only allow one particular type of ion to pass. These include the potassium, sodium, calcium and chloride channels. Cation channels allow both K⁺ and Na⁺ ions to pass in opposite directions across the membrane through the same channel. This property implies that most channels are quite narrow so that the channel protein can ‘look’ carefully at the ion as it passes through the channel in order to determine its chemical properties. In general, this means there are specific binding sites for the selected ions in the channel and they pass single file through the channel (Figure 2).

Figure 1 Five main types of ion channels based on their ion selectivity. Arrows indicate the primary direction of ion movement in or out of the cell in adult neurons. In most other cell types, as well as developing neurons, chloride ions move out of the cell.

Another key property of ion channels is known as gating, which refers to the ability of a channel to open or close in response to a specific stimulus.

Figure 2 Gating of a potassium ion channel. As soon as the gates open, potassium ions start streaming out of the cell. The ions pass through the channel single file together with some water molecules (not shown). There is a high concentration of potassium ions inside the cell and a high concentration of sodium ions outside the cells. The reaction scheme on the right indicates the state of the channel. In this example the channel can be in one of two states: open or closed. When the channel is closed some ions remain bound to specific ion binding sites within the channel. The green circles represent potassium ions, which can pass through the channel, and the red circles represent sodium ions, which are excluded. Start the animation by clicking the ‘open’ button.

Ion channels are found in the cell membranes of all mammalian cells and in the cell membranes of almost all living organisms, and many viruses. At rest, in a typical cell, only a small number of the channels present in the membrane are actually open and passing ions. Collectively, these channels are known as the leak channels. These leak channels are predominantly K⁺ selective. As a consequence, at rest, the cell membrane is predominantly permeable to K⁺ ions.

Ion channels are of particular interest because of their key role in generating electrical excitation in neurons, muscle cells and some endocrine cells, which is described in later chapters. During this electrical signaling many of the channels that were closed become active.

One obvious question is why is it necessary to have a specific channel to pass potassium ions across the membrane and a completely different channel to pass sodium ions when they could both pass through a non-selective cation channel? In part the answer relates to the role of ion channels in mediating current flow across the membrane to produce electrical activity. Electrons flowing in a wire can carry current in both directions. Over the normal range of membrane potentials, the potassium and sodium channels typically carry current in only one direction, which is determined by the direction of the ion concentration gradients (Figure 3).

Figure 3 Direction of net potassium ion (green) and sodium ion (red) flow through potassium and sodium selective channels. The direction of electrical current flow through these channels is indicated by the arrows.

It is necessary to have both potassium and sodium channels in order to create the opposing electrical currents that generate electrical excitability. Potassium channels mediate the outward flux of potassium ions, known as an outward current, and sodium channels mediate an inward flux of sodium ions, known as an inward current. The direction of the current flow determines whether the membrane potential becomes more negative or more positive. Having two different types of ion selective channels allows the cell to manipulate the membrane potential for electrical signaling or other purposes.

Other Cell Membrane Channels

Water channels selectively pass water molecules across the membrane. They are generally always open and the regulation of the water permeability of the cell membrane is achieved by increasing or decreasing the number of channels in the cell membrane. These channels are discussed later in this chapter.

Gap junction channels are very large non-selective channels, which freely pass ions and small metabolites between cells. Because these channels connect the cytoplasm of one cell to another there is no net loss of small metabolites or ions from the cells. Gap junction channels do not normally open to the extracellular solution.