- Key People:
- Erwin Neher
- Bert Sakmann
- Roderick MacKinnon
ion channel
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What is an ion channel?
An ion channel is a protein that virtually all living cells express, creating a pathway for charged ions from dissolved salts, such as potassium, sodium, calcium, and chloride, to pass through the otherwise impermeable lipid cell membrane.
Ions flow passively through channels toward equilibrium, driven by electrical (voltage) or chemical (concentration) gradients. Most ion channels are gated, opening and closing either spontaneously or in response to a specific stimulus, like the binding of a small molecule or a change in voltage.
These channels are essential for various physiological processes, including nerve signal transmission, heart and skeletal muscle contraction, and secretion in the pancreas. They also regulate cytoplasmic calcium concentration and acidification of specific subcellular compartments.
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Where are ion channels found in the body?
Ion channels are proteins present in virtually all living cells. They facilitate the passage of charged ions, such as sodium and potassium, through the cell membrane.
Ion channels are essential for various physiological processes. For example, they enable the operation of the nervous system, muscle contraction, and secretion in the pancreas. They are also present in intracellular organelles, where they regulate cytoplasmic calcium concentration and acidification. In nerve cells, ion channels help create action potentials, which are critical for nerve impulses. In muscle cells, they open to allow the entry of positive ions, triggering a self-generating action potential that leads to muscle contraction.
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What do ion channels do for cells?
Ion channels are proteins present in nearly all living cells. They create a pathway for charged ions, such as potassium, sodium, calcium, and chloride, to pass through the cell membrane.
Ions flow through channels toward equilibrium, driven by voltage or chemical gradients. The development of ion channels may have given single-celled organisms an evolutionary advantage by allowing them to regulate their volume when environmental conditions change.
Many ion channels are gated, opening or closing spontaneously or in response to a stimulus. Most are selective, allowing only certain ions to pass through. The flow of ions through open channels creates an electrical current that alters the voltage across the membrane by changing the distribution of charge.
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How do ions move through ion channels?
Ions move through ion channels via diffusion, traveling down a concentration gradient from areas of high concentration to areas of low concentration. This movement occurs through open channels, which are pores formed by intrinsic proteins that traverse the lipid bilayer of a cell membrane.
Most ion channels are gated, opening and closing either spontaneously or in response to specific stimuli such as voltage changes or the binding of molecules. Ion channels are selective, allowing only certain ions to pass through based on charge and size. Narrow, highly selective ion channels mimic the ion's water environment by lining the conducting pore with polarized carbonyl oxygen atoms.
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What are some examples of ions that use ion channels?
Ion channels are proteins that create pathways for ions, such as sodium, potassium, calcium, and chloride, to pass through cell membranes.
Examples of ions that use ion channels:
* Sodium ions Transient influx of positive ions like sodium through voltage-gated channels causes brief membrane depolarizations known as action potentials.
* Potassium ions Following membrane depolarization, an outward flow of (K^+) occurs through the delayed rectifier channel, counteracting the effects of (Na^+).
* Calcium ions Action potentials trigger physiological effects by opening voltage-gated calcium-selective ion channels, which increases the intracellular calcium concentration.
* Chloride ions Some channels exhibit relative selectivity, allowing positively charged cations to pass through while excluding negatively charged anions.2 Britannica SourcesCreated from Britannica articles using AI. AI can make mistakes, so verify using Britannica articles. -
How do problems with ion channels affect human health?
Ion channel malfunctions can disrupt key physiological processes, leading to various disorders. These disorders, known as channelopathies, include ataxia, diabetes mellitus, certain types of epilepsy, and cardiac arrhythmias.
Many natural toxins target ion channels, such as tetrodotoxin, alpha-bungarotoxin, strychnine, and d-tubocurarine. Therapeutic drugs, like local anesthetics and benzodiazepines, can also modulate ion channel activity.
Genetic variations in sodium and potassium-selective channels can cause long-QT syndrome, characterized by prolonged cardiac myocyte action potentials and potentially fatal arrhythmias. Mutations in ATP-sensitive potassium channels, which regulate insulin secretion in the pancreas, can result in diabetes mellitus.
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ion channel, protein expressed by virtually all living cells that creates a pathway for charged ions from dissolved salts, including sodium, potassium, calcium, and chloride ions, to pass through the otherwise impermeant lipid cell membrane. Operation of cells in the nervous system, contraction of the heart and of skeletal muscle, and secretion in the pancreas are examples of physiological processes that require ion channels. In addition, ion channels in the membranes of intracellular organelles are important for regulating cytoplasmic calcium concentration and acidification of specific subcellular compartments (e.g., lysosomes).
Evolution and selectivity
Ions flow passively through channels toward equilibrium. This movement may be driven by electrical (voltage) or chemical (concentration) gradients. The ability to alter ion flow as a result of the development of ion channels may have provided an evolutionary advantage by allowing single-celled organisms to regulate their volume in the face of environmental changes. Through subsequent evolution, ion channels have come to play essential roles in cellular secretion and electrical signaling.
Most ion channels are gated—that is, they open and close either spontaneously or in response to a specific stimulus, such as the binding of a small molecule to the channel protein (ligand-gated ion channels) or a change in voltage across the membrane that is sensed by charged segments of the channel protein (voltage-gated ion channels). In addition, most ion channels are selective, allowing only certain ions to pass through. Some channels conduct only one type of ion (e.g., potassium), whereas other channels exhibit relative selectivity—for example, allowing positively charged cations to pass through while excluding negatively charged anions. Cells in higher organisms may express more than 100 different types of ion channel, each with different selectivity and different gating properties.
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Function and structure
The flow of charged ions through open channels represents an electrical current that changes the voltage across the membrane by altering the distribution of charge. In excitable cells, voltage-gated channels that allow transient influx of positive ions (e.g., sodium and calcium ions) underlie brief depolarizations of the membrane known as action potentials. Action potentials can be transmitted rapidly over long distances, allowing for coordination and precise timing of physiological outputs. In nearly all cases, action potentials trigger downstream physiological effects, such as secretion or muscle contraction, by opening voltage-gated calcium-selective ion channels and elevating intracellular calcium concentration.
The amino acid sequences of many different ion channel proteins have been determined, and in a few cases the X-ray crystal structure of the channel is known as well. Based on their structure, the majority of ion channels can be classified into six or seven superfamilies. For potassium-selective channels, which are among the best-characterized ion channels, four homologous transmembrane subunits come together to create a tunnel, known as the conducting pore, that provides a polar pathway through the nonpolar lipid membrane. Other channel types require either three or five homologous subunits to generate the central conducting pore. In solution, ions are stabilized by polarized water molecules in the surrounding environment. Narrow, highly selective ion channels mimic the water environment by lining the conducting pore with polarized carbonyl oxygen atoms. Less-selective channels form pores with a diameter large enough that ions and water molecules may pass through together.
Toxins and disease
Many natural toxins target ion channels. Examples include the voltage-gated sodium channel blocker tetrodotoxin, which is produced by bacteria resident in puffers (blowfish) and several other organisms; the irreversible nicotinic acetylcholine receptor antagonist alpha-bungarotoxin, from the venom of snakes in the genus Bungarus (kraits); and plant-derived alkaloids, such as strychnine and d-tubocurarine, which inhibit the activation of ion channels that are opened by the neurotransmitters glycine and acetylcholine, respectively. In addition, a large number of therapeutic drugs, including local anesthetics, benzodiazepines, and sulfonylurea derivatives, act directly or indirectly to modulate ion channel activity.
Inherited mutations in ion channel genes and in genes encoding proteins that regulate ion channel activity have been implicated in a number of diseases, including ataxia (the inability to coordinate voluntary muscle movements), diabetes mellitus, certain types of epilepsy, and cardiac arrhythmias (irregularities in heartbeat). For example, genetic variations in sodium-selective and potassium-selective channels, or in their associated regulatory subunits, underlie some forms of long-QT syndrome. This syndrome is characterized by a prolongation in the depolarization time-course of cardiac myocyte action potentials, which can lead to fatal arrhythmias. In addition, mutations in adenosine triphosphate (ATP)-sensitive potassium channels that control insulin secretion from cells in the pancreas underlie some forms of diabetes mellitus.
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Role in research
Ongoing basic research on ion channels seeks to understand the structural basis for permeability, ion selectivity, and gating at the molecular level. Research efforts also attempt to answer questions about the cellular regulation of ion channel protein synthesis and about the subcellular distribution and ultimate degradation of channels. In addition, compounds with greater specificity and potency for channels involved in pain sensation, cardiovascular disease, and other pathological conditions are potential sources for drug development.