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Ion Channel

Certain cells, commonly called excitable cells, are unique because of their ability to generate electrical signals. Although several types of excitable cells exist — including neurons, muscle cells, and touch receptor cells — all of them use ion channel receptors to convert chemical or mechanical messages into electrical signals.

Like all cells, an excitable cell maintains a different concentration of ions in its cytoplasm than exists in its extracellular environment. Together, these concentration differences create a small electrical potential across the plasma membrane. Then, when conditions are right, specialized channels in the plasma membrane open and allow rapid ion movement into or out of the cell, and this movement creates an electrical signal. But what do these channels look like, and how do they function? Also, how do the electrical signals generated by excitable cells differ from the other types of signals involved in cellular communication?

What Are Ion Channel Receptors?

Ion channel receptors are usually multimeric proteins located in the plasma membrane. Each of these proteins arranges itself so that it forms a passageway or pore extending from one side of the membrane to the other. These passageways, or ion channels, have the ability to open and close in response to chemical or mechanical signals. When an ion channel is open, ions move into or out of the cell in single-file fashion. Individual ion channels are specific to particular ions, meaning that they usually allow only a single type of ion to pass through them. Both the amino acids that line a channel and the physical width of the channel determine which ions are able to wiggle through from the cell exterior to its interior, and vice versa. The opening of an ion channel is a fleeting event. Within a few milliseconds of opening, most ion channels close and enter a resting state, where they are unresponsive to signals for a short period of time (Figure 1).

A three-part schematic shows different views of the acetylcholine receptor in a horizontal plasma membrane. The extracellular environment is above the membrane, and the intracellular environment is below the membrane. The receptor is made up of five vertical green cylindrical structures that span the plasma membrane. The cylinders are arranged in a circle, and one of the cylinders is positioned at the front. The left side of the diagram shows the channel in an inactive, closed conformation with the front cylinder in place. The inactive, closed channel is also shown in the center, but the front cylinder has been removed to show that bulges in two of the cylinders block the pore. An active, open conformation of the channel is shown at the right with two round, blue acetylcholine molecules bound to the extracellular side of the channel, and smaller red, round ions moving through the open aqueous channel from the extracellular space to the inside of the cell.
Figure 1: An example of ion channel receptor activation
An acetylcholine receptor (green) forms a gated ion channel in the plasma membrane. This receptor is a membrane protein with an aqueous pore, meaning it allows soluble materials to travel across the plasma membrane when open. When no external signal is present, the pore is closed (center). When acetylcholine molecules (blue) bind to the receptor, this triggers a conformational change that opens the aqueous pore and allows ions (red) to flow into the cell.
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How Are Electrical Signals Propagated?

A two-part schematic shows a comparison between two different types of membrane receptors as they respond to an extracellular signal. In panel A, an extracellular ligand binds to a G-protein-coupled receptor and initiates a relatively slow activation sequence. In panel B, an extracellular ligand binds to an ion channel receptor and initiates a much more rapid electrical response. In both illustrations, each protein receptor is shown embedded in a simplified cell membrane, and the cell membrane is represented as a strip of parallel, vertical grey lines. The area above the membrane represents the extracellular environment, and the area below the membrane represents the intracellular environment, or the area contained inside the cell. The G-protein-coupled receptor and the ion channel receptor both span the cell membrane multiple times and have extracellular and intracellular regions.
Figure 2: Comparing the activation of an ion channel receptor with that of a G-protein-coupled receptor
Activation of both a G-protein-coupled receptor (a) and an ion channel receptor (b) cause a conformational change in the receptor protein. G protein activation can lead to multiple intracellular events through a variety of intracellular proteins, and this signaling can take seconds to minutes. When a G protein activates transcription, this can take up to 20 minutes. In contrast, ion channel receptors open pores in the cell membrane, causing the formation of electrical current. This receptor activation therefore causes a much faster response within the cell, on the order of milliseconds.
© 2008 Nature Publishing Group Moreau, C. J. et al. Coupling ion channels to receptors for biomolecule sensing. Nature Nanotechnology 3, 620-625 (2008) doi:10.1038/nnano.2008.242. All rights reserved. View Terms of Use
The opening of ion channels alters the charge distribution across the plasma membrane. Recall that the ionic composition of the cytoplasm is quite different from that of the extracellular environment. For instance, the concentration of sodium ions in the cytoplasm is far lower than that in the cell's exterior environment. Conversely, potassium ions exist at higher concentrations within a cell than outside it. Such differences create a so-called electrochemical gradient, which is a combination of a chemical gradient and a charge gradient. The opening of ion channels permits the ions on either side of the plasma membrane to flow down this dual gradient. The exact direction of flow varies by ion type, and it depends on both the concentration difference and the voltage difference for each variety of ion. This ion flow results in the production of an electrical signal. The actual number of ions required to change the voltage across the membrane is quite small. During the short times that an ion channel is open, the concentration of a particular ion in the cytoplasm as a whole does not change significantly, only the concentration in the immediate vicinity of the channel. In excitable cells, the electrical signal initiated by ion channel receptor activity travels rapidly over the surface of the cell due to the opening of other ion channels that are sensitive to the voltage change caused by the initial channel opening.

Electrical signals travel much more rapidly than chemical signals, which depend on the process of molecular diffusion. As a consequence, excitable cells respond to signals much more rapidly than cells that rely solely on chemical signals (Figure 2). In fact, an electrical signal can traverse the entire length of a human nerve cell — a distance of as much as one meter — within only milliseconds.

How Do Different Types of Excitable Cells Work?

Neurons, muscle cells, and touch receptor cells are all excitable cells — which means they all have the capacity to transmit electrical signals. Each of these cells also has ion channel receptors clustered on a particular part of its surface. For example, the receptors that respond to chemical signals are generally located at synapses — or points of near contact between adjacent cells.

Of the various types of excitable cells that respond to chemical signals, neurons are perhaps the most familiar. When electrical signals reach the end of neurons, they trigger the release of chemical messengers called neurotransmitters. Each neurotransmitter then diffuses from its point of release on one side of the synapse to the cell on the other side of the synapse. If the neurotransmitter binds to an ion channel receptor on the target cell, the related ion channel opens, and an electrical signal propagates itself along the length of the target cell.

Neurons have ion channel receptors specific to many kinds of neurotransmitters. Some of these neurotransmitters act in an excitatory capacity, bringing their target cells ever closer to signal propagation. Other neurotransmitters exert an inhibitory effect, counteracting any excitatory input and lessening the chance that the target cell will fire.

Skeletal muscle cells also rely on chemical signals in order to generate electrical signals. These cells have synapses that are packed with receptors for acetylcholine, which is the primary neurotransmitter released by motor neurons. When acetylcholine binds to the receptors on a skeletal muscle cell, ion channels in that cell open, and this launches a sequence of events that results in contraction of the cell.

In contrast to neurons and skeletal muscle cells, some excitable cells have ion channels that open in response to mechanical stimuli rather than chemical signals. These include the hair cells of the mammalian inner ear and the touch receptor cells of both human finger pads and Venus fly traps. Cells that respond to touch have their ion channel receptors clustered at the position where contact usually occurs.


Excitable cells, such as fast-acting neurons and muscle cells, have specialized channels that open in response to a signal and permit rapid ion movement across the cell membrane. The opening of just a single ion channel alters the electrical charge on both sides of the membrane. The resulting charge differential then causes adjacent voltage-sensitive channels to open in chain-reaction fashion, creating a self-propagating electrical signal that travels down the entire length of the cell. Sometimes, this sequence of events is triggered when a chemical signal — such as a neurotransmitter — binds to an ion channel receptor on cell's surface. Other times, a cell's ion channels open in response to mechanical (rather than chemical) stimuli.


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