Calcium channel

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A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, [1] which are a type of calcium channel regulated by changes in membrane potential. Some calcium channels are regulated by the binding of a ligand. [2] [3] Other calcium channels can also be regulated by both voltage and ligands to provide precise control over ion flow. Some cation channels allow calcium as well as other cations to pass through the membrane.

Contents

Calcium channels can participate in the creation of action potentials across cell membranes. Calcium channels can also be used to release calcium ions as second messengers within the cell, affecting downstream signaling pathways.    

Comparison tables

The following tables explain gating, gene, location and function of different types of calcium channels, both voltage and ligand-gated.

Voltage-gated

TypeVoltageα1 subunit (gene name)Associated subunitsMost often found in
L-type calcium channel ("Long-Lasting" AKA "DHP Receptor")HVA (high voltage activated) Cav1.1 ( CACNA1S )
Cav1.2 ( CACNA1C ) Cav1.3 ( CACNA1D )
Cav1.4 ( CACNA1F )
α2δ, β, γSkeletal muscle, smooth muscle, bone (osteoblasts), ventricular myocytes** (responsible for prolonged action potential in cardiac cell; also termed DHP receptors), dendrites and dendritic spines of cortical neurons
N-type calcium channel ("Neural"/"Non-L")HVA (high-voltage-activated) Cav2.2 ( CACNA1B )α2δ/β1, β3, β4, possibly γThroughout the brain and peripheral nervous system.
P-type calcium channel ("Purkinje") /Q-type calcium channel HVA (high voltage activated) Cav2.1 ( CACNA1A )α2δ, β, possibly γ Purkinje neurons in the cerebellum / Cerebellar granule cells
R-type calcium channel ("Residual")intermediate-voltage-activated Cav2.3 ( CACNA1E )α2δ, β, possibly γ Cerebellar granule cells, other neurons
T-type calcium channel ("Transient")low-voltage-activated Cav3.1 ( CACNA1G )
Cav3.2 ( CACNA1H )
Cav3.3 ( CACNA1I )
neurons, cells that have pacemaker activity, bone (osteocytes), thalamus (thalamus)

Ligand-gated

TypeGated byGeneLocationFunction
IP3 receptor IP3 ITPR1, ITPR2, ITPR3 ER/SR Releases calcium from ER/SR in response to IP3 by e.g. GPCRs [4]
Ryanodine receptor dihydropyridine receptors in T-tubules and increased intracellular calcium (Calcium Induced Calcium Release - CICR)RYR1, RYR2, RYR3 ER/SR Calcium-induced calcium release in myocytes [4]
Two-pore channel Nicotinic acid adenine dinucleotide phosphate (NAADP)TPCN1, TPCN2endosomal/lysosomal membranesNAADP-activated calcium transport across endosomal/lysosomal membranes [5]
store-operated channels [6] indirectly by ER/SR depletion of calcium [4] ORAI1, ORAI2, ORAI3 plasma membrane Provides calcium signaling to the cytoplasm [7]

Non-selective Channels Permeable to Calcium

There are several cation channel families that allow positively charged ions including calcium to pass through. These include P2X receptors, Transient Receptor Potential (TRP) channels, Cyclic nucleotide-gated (CNG) channels, Acid-sensing ion channels, and SOC channels. [8] These channels can be regulated by membrane voltage potentials, ligands, and/or other cellular conditions. Cat-Sper channels, found in mammalian sperm, are one example of this as they are voltage gated and ligand regulated. [9]

Pharmacology

Depiction of binding sites of various antagonistic drugs in the L-type calcium channel. L-type calcium channel.jpg
Depiction of binding sites of various antagonistic drugs in the L-type calcium channel.

L-type calcium channel blockers are used to treat hypertension. In most areas of the body, depolarization is mediated by sodium influx into a cell; changing the calcium permeability has little effect on action potentials. However, in many smooth muscle tissues, depolarization is mediated primarily by calcium influx into the cell. L-type calcium channel blockers selectively inhibit these action potentials in smooth muscle which leads to dilation of blood vessels; this in turn corrects hypertension. [10]

T-type calcium channel blockers are used to treat epilepsy. Increased calcium conductance in the neurons leads to increased depolarization and excitability. This leads to a greater predisposition to epileptic episodes. Calcium channel blockers reduce the neuronal calcium conductance and reduce the likelihood of experiencing epileptic attacks. [11]

See also

Related Research Articles

<span class="mw-page-title-main">Ion channel</span> Pore-forming membrane protein

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

<span class="mw-page-title-main">Action potential</span> Neuron communication by electric impulses

An action potential occurs when the membrane potential of a specific cell rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and in some plant cells. Certain endocrine cells such as pancreatic beta cells, and certain cells of the anterior pituitary gland are also excitable cells.

An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. IPSPs were first investigated in motorneurons by David P. C. Lloyd, John Eccles and Rodolfo Llinás in the 1950s and 1960s. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential. IPSPs can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell to cell signalling. Inhibitory presynaptic neurons release neurotransmitters that then bind to the postsynaptic receptors; this induces a change in the permeability of the postsynaptic neuronal membrane to particular ions. An electric current that changes the postsynaptic membrane potential to create a more negative postsynaptic potential is generated, i.e. the postsynaptic membrane potential becomes more negative than the resting membrane potential, and this is called hyperpolarisation. To generate an action potential, the postsynaptic membrane must depolarize—the membrane potential must reach a voltage threshold more positive than the resting membrane potential. Therefore, hyperpolarisation of the postsynaptic membrane makes it less likely for depolarisation to sufficiently occur to generate an action potential in the postsynaptic neurone.

<span class="mw-page-title-main">Membrane potential</span> Type of physical quantity

Membrane potential is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges to move from the internal to exterior cellular environments and vice versa, as long as there is no acquisition of kinetic energy or the production of radiation. The concentration gradients of the charges directly determine this energy requirement. For the exterior of the cell, typical values of membrane potential, normally given in units of milli volts and denoted as mV, range from –80 mV to –40 mV.

<span class="mw-page-title-main">Cardiac action potential</span> Biological process in the heart

The cardiac action potential is a brief change in voltage across the cell membrane of heart cells. This is caused by the movement of charged atoms between the inside and outside of the cell, through proteins called ion channels. The cardiac action potential differs from action potentials found in other types of electrically excitable cells, such as nerves. Action potentials also vary within the heart; this is due to the presence of different ion channels in different cells.

Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.

<span class="mw-page-title-main">End-plate potential</span>

End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters are exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.

<span class="mw-page-title-main">Voltage-gated ion channel</span> Type of ion channel transmembrane protein

Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as 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. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl) ions have been identified. The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane.

<span class="mw-page-title-main">Ligand-gated ion channel</span> Type of ion channel transmembrane protein

Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter.

Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. These channels are slightly permeable to sodium ions, so they are also called Ca2+–Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

<span class="mw-page-title-main">Inward-rectifier potassium channel</span> Group of transmembrane proteins that passively transport potassium ions

Inward-rectifier potassium channels (Kir, IRK) are a specific lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are activated by phosphatidylinositol 4,5-bisphosphate (PIP2). The malfunction of the channels has been implicated in several diseases. IRK channels possess a pore domain, homologous to that of voltage-gated ion channels, and flanking transmembrane segments (TMSs). They may exist in the membrane as homo- or heterooligomers and each monomer possesses between 2 and 4 TMSs. In terms of function, these proteins transport potassium (K+), with a greater tendency for K+ uptake than K+ export. The process of inward-rectification was discovered by Denis Noble in cardiac muscle cells in 1960s and by Richard Adrian and Alan Hodgkin in 1970 in skeletal muscle cells.

Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels.

The P-type calcium channel is a type of voltage-dependent calcium channel. Similar to many other high-voltage-gated calcium channels, the α1 subunit determines most of the channel's properties. The 'P' signifies cerebellar Purkinje cells, referring to the channel's initial site of discovery. P-type calcium channels play a similar role to the N-type calcium channel in neurotransmitter release at the presynaptic terminal and in neuronal integration in many neuronal types.

<span class="mw-page-title-main">L-type calcium channel</span> Family of transport proteins

The L-type calcium channel is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This channel has four isoforms: Cav1.1, Cav1.2, Cav1.3, and Cav1.4.

Light-gated ion channels are a family of ion channels regulated by electromagnetic radiation. Other gating mechanisms for ion channels include voltage-gated ion channels, ligand-gated ion channels, mechanosensitive ion channels, and temperature-gated ion channels. Most light-gated ion channels have been synthesized in the laboratory for study, although two naturally occurring examples, channelrhodopsin and anion-conducting channelrhodopsin, are currently known. Photoreceptor proteins, which act in a similar manner to light-gated ion channels, are generally classified instead as G protein-coupled receptors.

<span class="mw-page-title-main">TRPM5</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene.

<span class="mw-page-title-main">TRPM8</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.

<span class="mw-page-title-main">Channel blocker</span> Molecule able to block protein channels, frequently used as pharmaceutical

A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, anions, amino acids, and other chemicals. These blockers act as ion channel antagonists, preventing the response that is normally provided by the opening of the channel.

<span class="mw-page-title-main">Gating (electrophysiology)</span>

In electrophysiology, the term gating refers to the opening (activation) or closing of ion channels. This change in conformation is a response to changes in transmembrane voltage.

References

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