Voltage-gated ion channel
Encyclopedia
Voltage-gated ion channels are a class of transmembrane
ion channel
s that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neuron
s, but are common in many types of cells
.
They have a crucial role in excitable neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change
. Found along the axon
and at the synapse
, voltage-gated ion channels directionally propagate electrical signals.
s. The channels tend to be ion-specific, although similarly sized and charged ions may sometimes travel through them.
Examples include:
structural studies of a potassium channel
, assuming that this structure remains intact in the corresponding plasma membrane
, it is possible to surmise that when a potential difference is introduced over the membrane, the associated electromagnetic field
induces a conformational change in the potassium channel. The conformational change distorts the shape of the channel proteins sufficiently such that the cavity, or channel, opens to admit ion influx or efflux to occur across the membrane, down its electrochemical gradient. This subsequently generates an electrical current sufficient to depolarise the cell membrane.
Voltage-gated sodium channels and calcium channels
are made up of a single polypeptide with four homologous domains. Each domain contains 6 membrane spanning alpha helices. One of these helices, S4, is the voltage sensing helix. It has many positive charges such that a high positive charge outside the cell repels the helix, keeping the channel in its closed state. Depolarization of the cell interior causes the helix to move, inducing a conformational change such that ions may flow through the channel (the open state). Potassium channels function in a similar way, with the exception that they are composed of four separate polypeptide chains, each comprising one domain.
The voltage-sensitive protein domain
of these channels (the "voltage sensor") generally contains a region composed of S3b and S4 helices, known as the "paddle" due to its shape, which appears to be a conserved sequence
, interchangeable across a wide variety of cells and species. Genetic engineering
of the paddle region from a species of volcano-dwelling archaebacteria into rat brain potassium channels results in a fully functional ion channel, as long as the whole intact paddle is replaced. This "modularity" allows use of simple and inexpensive model systems to study the function of this region, its role in disease, and pharmaceutical control of its behavior rather than being limited to poorly characterized, expensive, and/or difficult to study preparations.
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, but are common in many types of cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
.
They have a crucial role in excitable neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change
Voltage drop
Voltage drop is the reduction in voltage in the passive elements of an electrical circuit. Voltage drops across conductors, contacts, connectors and source internal resistances are undesired as they reduce the supplied voltage while voltage drops across loads and other electrical and electronic...
. Found along the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
and at the synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
, voltage-gated ion channels directionally propagate electrical signals.
Structure
They generally are composed of several subunits arranged in such a way that there is a central pore through which ions can travel down their electrochemical gradientElectrochemical gradient
An electrochemical gradient is a spatial variation of both electrical potential and chemical concentration across a membrane; that is, a combination of the membrane potential and the pH gradient...
s. The channels tend to be ion-specific, although similarly sized and charged ions may sometimes travel through them.
Examples include:
- the sodium and potassiumPotassium channelIn the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
voltage-gated channels of nerve and muscle. - the voltage-gated calcium channels that play a role in neurotransmitter release in pre-synaptic nerve endings.
Mechanism
From crystallographicX-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
structural studies of a potassium channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
, assuming that this structure remains intact in the corresponding plasma membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
, it is possible to surmise that when a potential difference is introduced over the membrane, the associated electromagnetic field
Electromagnetic field
An electromagnetic field is a physical field produced by moving electrically charged objects. It affects the behavior of charged objects in the vicinity of the field. The electromagnetic field extends indefinitely throughout space and describes the electromagnetic interaction...
induces a conformational change in the potassium channel. The conformational change distorts the shape of the channel proteins sufficiently such that the cavity, or channel, opens to admit ion influx or efflux to occur across the membrane, down its electrochemical gradient. This subsequently generates an electrical current sufficient to depolarise the cell membrane.
Voltage-gated sodium channels and calcium channels
Voltage-dependent calcium channel
Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...
are made up of a single polypeptide with four homologous domains. Each domain contains 6 membrane spanning alpha helices. One of these helices, S4, is the voltage sensing helix. It has many positive charges such that a high positive charge outside the cell repels the helix, keeping the channel in its closed state. Depolarization of the cell interior causes the helix to move, inducing a conformational change such that ions may flow through the channel (the open state). Potassium channels function in a similar way, with the exception that they are composed of four separate polypeptide chains, each comprising one domain.
The voltage-sensitive protein domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
of these channels (the "voltage sensor") generally contains a region composed of S3b and S4 helices, known as the "paddle" due to its shape, which appears to be a conserved sequence
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...
, interchangeable across a wide variety of cells and species. Genetic engineering
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
of the paddle region from a species of volcano-dwelling archaebacteria into rat brain potassium channels results in a fully functional ion channel, as long as the whole intact paddle is replaced. This "modularity" allows use of simple and inexpensive model systems to study the function of this region, its role in disease, and pharmaceutical control of its behavior rather than being limited to poorly characterized, expensive, and/or difficult to study preparations.
External links
- IUPHAR-DB Voltage-gated ion channel subunits
- The IUPHAR Compendium of Voltage-gated Ion Channels 2005
See also
- Ion channelIon channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
- Voltage-dependent calcium channelVoltage-dependent calcium channelVoltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...
- Voltage-gated proton channelVoltage-gated proton channelVoltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells...
- Voltage-gated potassium channelVoltage-gated potassium channelVoltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....
- Sodium ion channelSodium ion channelSodium channels are integral membrane proteins that form ion channels, conducting sodium ions through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e...
- Potassium channelPotassium channelIn the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
- Catecholaminergic polymorphic ventricular tachycardiaCatecholaminergic polymorphic ventricular tachycardiaCatecholaminergic Polymorphic Ventricular Tachycardia is an electrophysiological disorder of the heart that occurs in genetically predisposed individuals...