Voltage-dependent calcium channel
Encyclopedia
Voltage-dependent calcium channels (VDCC) are a group of voltage-gated
ion channel
s found in excitable cells (e.g., muscle, glial cell
s, neuron
s, etc.) with a permeability
to the 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. At physiologic or resting membrane potential
, VDCCs are normally closed. They are activated (i.e., opened) at depolarized
membrane potential
s and this is the source of the "voltage-dependent" epithet
. Activation of particular VDCCs allows Ca2+
entry into the cell, which, depending on the cell type, results in muscular contraction
, excitation of neurons, up-regulation of gene expression
, or release of hormone
s or neurotransmitter
s.
s. High-voltage-gated calcium channels include the neural
N-type channel blocked by ω-conotoxin
GVIA, the R-type channel (R stands for Resistant to the other blockers and toxins, except SNX-482
) involved in poorly defined processes in the brain
, the closely related P/Q-type channel blocked by ω-agatoxins, and the dihydropyridine-sensitive L-type channels responsible for excitation-contraction coupling of skeletal
, smooth
, and cardiac muscle
and for hormone secretion in endocrine cells.
Co-expression of the α2δ enhances the level of expression of the α1 subunit and causes an increase in current amplitude, faster activation and inactivation kinetics and a hyperpolarizing shift in the voltage dependence of inactivation. Some of these effects are observed in the absence of the beta subunit, whereas, in other cases, the co-expression of beta is required.
The α2δ-1 and α2δ-2 subunits are the binding site for at least two anticonvulsant drugs, gabapentin
(Neurontin) and pregabalin
(Lyrica), that also find use in treating chronic neuropathic pain.
It is hypothesized that the cytosolic β subunit has a major role in stabilizing the final α1 subunit conformation and delivering it to the cell membrane by its ability to mask an endoplasmic reticulum
retention signal in the α1 subunit. The endoplasmic retention brake is contained in the I-II loop in the α1 subunit that becomes masked when the β subunit binds. Therefore the β subunit functions initially to regulate the current density by controlling the amount of α1 subunit expressed at the cell membrane.
In addition to this trafficking role, the β subunit has the added important functions of regulating the activation and inactivation kinetics, and hyperpolarizing the voltage-dependence for activation of the α1 subunit pore, so that more current passes for smaller depolarization
s. The β subunit has effects on the kinetics of the cardiac α1C in Xenopus laevis oocytes co-expressed with β subunits. The β subunit acts as an important modulator of channel electrophysiological properties.
Until very recently, the interaction between a highly conserved 18-amino acid
region on the α1 subunit intracellular linker between domains I and II (the Alpha Interaction Domain, AID) and a region on the GK domain of the β subunit (Alpha Interaction Domain Binding Pocket) was thought to be solely responsible for the regulatory effects by the β subunit. Recently, it has been discovered that the SH3 domain of the β subunit also gives added regulatory effects on channel function, opening the possibility of the β subunit having multiple regulatory interactions with the α1 subunit pore. Furthermore, the AID sequence does not appear to contain an endoplasmic reticulum retention signal, and this may be located in other regions of the I-II α1 subunit linker.
There are 8 genes for gamma subunits:
cell is depolarized, it causes opening of the voltage-gated, or L-type, calcium channels. Depolarization may be brought about by stretching of the cell, agonist-binding its G protein-coupled receptor (GPCR), or autonomic nervous system
stimulation. Opening of the L-type calcium channel causes influx of extracellular Ca2+, which then binds calmodulin
. The activated calmodulin molecule activates myosin light-chain kinase
(MLCK), which phosphorylates the myosin
in thick filaments. Phosphorylated myosin is able to form crossbridges with actin
thin filaments, and the smooth muscle fiber (i.e., cell) contracts via the sliding filament mechanism
. (See reference for an illustration of the signaling cascade involving L-type calcium channels in smooth muscle).
L-type calcium channels are also enriched in the t-tubule
s of striated muscle
cells, i.e., skeletal and cardiac myofibers. When these cells are depolarized, the L-type calcium channels open as in smooth muscle. In skeletal muscle, the actual opening of the channel, which is mechanically gated to a calcium-release channel (a.k.a. ryanodine receptor
, or RYR) in the sarcoplasmic reticulum (SR), causes opening of the RYR. In cardiac muscle
, opening of the L-type calcium channel permits influx of calcium into the cell. The calcium binds to the calcium release channels (RYRs) in the SR, opening them; this phenomenon is called "calcium-induced calcium release
", or CICR. However the RYRs are opened, either through mechanical-gating or CICR, Ca2+ is released from the SR and is able to bind to troponin C
on the actin filaments. The muscles then contract through the sliding filament mechanism, causing shortening of sarcomeres and muscle contraction.
Voltage-gated ion channel
Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....
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 found in excitable cells (e.g., muscle, glial cell
Glial cell
Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
s, 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, etc.) with a permeability
Permeability (electromagnetism)
In electromagnetism, permeability is the measure of the ability of a material to support the formation of a magnetic field within itself. In other words, it is the degree of magnetization that a material obtains in response to an applied magnetic field. Magnetic permeability is typically...
to the ion Ca2+
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
. 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. At physiologic or resting membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...
, VDCCs are normally closed. They are activated (i.e., opened) at depolarized
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...
s and this is the source of the "voltage-dependent" epithet
Epithet
An epithet or byname is a descriptive term accompanying or occurring in place of a name and having entered common usage. It has various shades of meaning when applied to seemingly real or fictitious people, divinities, objects, and binomial nomenclature. It is also a descriptive title...
. Activation of particular VDCCs allows Ca2+
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
entry into the cell, which, depending on the cell type, results in muscular contraction
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
, excitation of neurons, up-regulation of gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
, or release of hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s or neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s.
Structure
Voltage-dependent calcium channels are formed as a complex of several different subunits: α1, α2δ, β1-4, and γ. The α1 subunit forms the ion conducting pore while the associated subunits have several functions including modulation of gating.Channel subunits
There are several different kinds of high-voltage-gated calcium channels (HVGCCs). They are structurally homologous among varying types; they are all similar, but not structurally identical. In the laboratory, it is possible to tell them apart by studying their physiological roles and/or inhibition by specific toxinToxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
s. High-voltage-gated calcium channels include the neural
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...
N-type channel blocked by ω-conotoxin
Conotoxin
A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of...
GVIA, the R-type channel (R stands for Resistant to the other blockers and toxins, except SNX-482
SNX-482
SNX-482 is a toxin from the tarantula Hysterocrates gigas. It acts as a high-affinity blocker of R-type Ca2+ channels, but at higher concentrations it can also block other Ca2+ channels and Na+ channels.- Homology :...
) involved in poorly defined processes in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, the closely related P/Q-type channel blocked by ω-agatoxins, and the dihydropyridine-sensitive L-type channels responsible for excitation-contraction coupling of skeletal
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
, smooth
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
, and cardiac muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
and for hormone secretion in endocrine cells.
| Current Type | 1,4-dihydropyridine sensitivity (DHP) | ω-conotoxin Conotoxin A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of... sensitivity (ω-CTX) |
ω-agatoxin sensitivity (ω-AGA) >- |
L-type | blocks | resistant | >- | N-type | resistant | blocks | >- | P/Q-type | resistant | resistant | >- | R-type | resistant | resistant | resistant |
α1 Subunit
The α1 subunit pore (~190 kDa in molecular mass) is the primary subunit necessary for channel functioning in the HVGCC, and consists of the characteristic four homologous I-IV domains containing six transmembrane α-helices each. The α1 subunit forms the Ca2+ selective pore, which contains voltage-sensing machinery and the drug/toxin-binding sites. A total of ten α1 subunits that have been identified in humans:| Type | Voltage | α1 subunit (gene name) | Associated subunits | Most often found in >- | L-type calcium channel L-type calcium channel The L-type calcium channel is a type of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. Like the others of this class, the α1 subunit is the one that determines most of the channel's properties.... ("Long-Lasting" AKA "DHP Receptor") |
HVA (high voltage activated) | Cav1.1 Cav1.1 Cav1.1 also known as the calcium channel, voltage-dependent, L type, alpha 1S subunit, , is a protein which in humans is encoded by the CACNA1S gene... Cav1.2 Cav1.3 Cav1.3 Cav1.3 also known as the calcium channel, voltage-dependent, L type, alpha 1D subunit , is a human gene.-External links:... Cav1.4 Cav1.4 Cav1.4 also known as the calcium channel, voltage-dependent, L type, alpha 1F subunit , is a human gene.-External Links:*... |
α2δ, β, γ | >- | HVA (high voltage activated) | Cav2.1 Cav2.1 The Cav2.1 P/Q voltage-dependent calcium channel is encoded by the gene.Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release,... |
α2δ, β, possibly γ | Cerebellar Cerebellum The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established... granule cell Granule cell In neuroscience, granule cells refer to tiny neurons that are around 10 micrometres in diameter. Granule cells are found within the granular layer of the cerebellum , the dentate gyrus of the... s >- | N-type calcium channel N-type calcium channel The N-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties... ("Neural"/"Non-L") |
HVA (high-voltage-activated) | Cav2.2 N-type calcium channel The N-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties... |
α2δ/β1, β3, β4, possibly γ | brain Brain The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,... and peripheral nervous system. >- | R-type calcium channel R-type calcium channel The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties... ("Residual") |
intermediate-voltage-activated | Cav2.3 R-type calcium channel The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties... |
α2δ, β, possibly γ | Cerebellar Cerebellum The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established... granule cell Granule cell In neuroscience, granule cells refer to tiny neurons that are around 10 micrometres in diameter. Granule cells are found within the granular layer of the cerebellum , the dentate gyrus of the... s, other neurons >- | T-type calcium channel T-type calcium channel The T-type calcium channel is a type of voltage-gated calcium channel. "T" stands for transient referring to the length of activation. As with other sub-types of voltage-gated calcium channel, the α1 subunit is the one that determines most of the channel's properties... ("Transient") |
low-voltage-activated | Cav3.1 CACNA1G Calcium channel, voltage-dependent, T type, alpha 1G subunit, also known as CACNA1G or Cav3.1 is a protein which in humans is encoded by the CACNA1G gene.- Function :... Cav3.2 CACNA1H Calcium channel, voltage-dependent, T type, alpha 1H subunit, also known as CACNA1H, is a protein which in humans is encoded by the CACNA1H gene.- Function :... Cav3.3 CACNA1I Calcium channel, voltage-dependent, T type, alpha 1I subunit, also known as CACNA1I or Cav3.3 is a protein which in humans is encoded by the CACNA1I gene.- Function :... |
neurons, cells that have pacemaker activity, bone (osteocytes) |
α2δ Subunit
The α2δ gene forms two subunits: α2 and δ (which are both the product of the same gene). They are linked to each other via a disulfide bond and have a combined molecular weight of 170 kDa. The α2 is the extracellular glycosylated subunit that interacts the most with the α1 subunit. The δ subunit has a single transmembrane region with a short intracellular portion, which serves to anchor the protein in the plasma membrane. There are 4 α2δ genes:- CACNA2D1CACNA2D1Voltage-dependent calcium channel subunit alpha-2/delta-1 is a protein that in humans is encoded by the CACNA2D1 gene.- External links :...
, - CACNA2D2CACNA2D2Voltage-dependent calcium channel subunit alpha2delta-2 is a protein that in humans is encoded by the CACNA2D2 gene....
, - ,
- .
Co-expression of the α2δ enhances the level of expression of the α1 subunit and causes an increase in current amplitude, faster activation and inactivation kinetics and a hyperpolarizing shift in the voltage dependence of inactivation. Some of these effects are observed in the absence of the beta subunit, whereas, in other cases, the co-expression of beta is required.
The α2δ-1 and α2δ-2 subunits are the binding site for at least two anticonvulsant drugs, gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...
(Neurontin) and pregabalin
Pregabalin
Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. It has also been found effective for generalized anxiety disorder and is approved for this use in the European Union. It was designed...
(Lyrica), that also find use in treating chronic neuropathic pain.
β Subunit
The intracellular β subunit (55 kDa) is an intracellular MAGUK-like protein (Membrane-Associated Guanylate Kinase) containing a guanylate kinase (GK) domain and an SH3 (src homology 3) domain. The guanylate kinase domain of the β subunit binds to the α1 subunit I-II cytoplasmic loop and regulates HVGCC activity. There are four known isoforms of the β subunit:- CACNB1CACNB1Voltage-dependent L-type calcium channel subunit beta-1 is a protein that in humans is encoded by the CACNB1 gene.- External links :...
, - CACNB2CACNB2Voltage-dependent L-type calcium channel subunit beta-2 is a protein that in humans is encoded by the CACNB2 gene.-External links:*...
, - CACNB3CACNB3Voltage-dependent L-type calcium channel subunit beta-3 is a protein that in humans is encoded by the CACNB3 gene....
, - CACNB4CACNB4Voltage-dependent L-type calcium channel subunit beta-4 is a protein that in humans is encoded by the CACNB4 gene.- Function :This gene encodes a member of the beta subunit family, a protein in the voltage-dependent calcium channel complex...
.
It is hypothesized that the cytosolic β subunit has a major role in stabilizing the final α1 subunit conformation and delivering it to the cell membrane by its ability to mask an endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
retention signal in the α1 subunit. The endoplasmic retention brake is contained in the I-II loop in the α1 subunit that becomes masked when the β subunit binds. Therefore the β subunit functions initially to regulate the current density by controlling the amount of α1 subunit expressed at the cell membrane.
In addition to this trafficking role, the β subunit has the added important functions of regulating the activation and inactivation kinetics, and hyperpolarizing the voltage-dependence for activation of the α1 subunit pore, so that more current passes for smaller depolarization
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
s. The β subunit has effects on the kinetics of the cardiac α1C in Xenopus laevis oocytes co-expressed with β subunits. The β subunit acts as an important modulator of channel electrophysiological properties.
Until very recently, the interaction between a highly conserved 18-amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
region on the α1 subunit intracellular linker between domains I and II (the Alpha Interaction Domain, AID) and a region on the GK domain of the β subunit (Alpha Interaction Domain Binding Pocket) was thought to be solely responsible for the regulatory effects by the β subunit. Recently, it has been discovered that the SH3 domain of the β subunit also gives added regulatory effects on channel function, opening the possibility of the β subunit having multiple regulatory interactions with the α1 subunit pore. Furthermore, the AID sequence does not appear to contain an endoplasmic reticulum retention signal, and this may be located in other regions of the I-II α1 subunit linker.
γ Subunit
The γ1 subunit is known to be associated with skeletal muscle VGCC complexes, but the evidence is inconclusive regarding other subtypes of calcium channel. The γ1 subunit glycoprotein (33 kDa) is composed of four transmembrane spanning helices. The γ1 subunit does not affect trafficking, and, for the most part, is not required to regulate the channel complex. However, γ2, γ3, γ4 and γ8 are also associated with AMPA glutamate receptors.There are 8 genes for gamma subunits:
- γ1CACNG1Voltage-dependent calcium channel gamma-1 subunit is a protein that in humans is encoded by the CACNG1 gene....
, - γ2CACNG2Calcium channel, voltage-dependent, gamma subunit 2, also known as CACNG2 or stargazin is a protein that in humans is encoded by the CACNG2 gene.-Function:...
, - γ3CACNG3Voltage-dependent calcium channel gamma-3 subunit is a protein that in humans is encoded by the CACNG3 gene....
, - γ4CACNG4Voltage-dependent calcium channel gamma-4 subunit is a protein that in humans is encoded by the CACNG4 gene....
, - ,
- ,
- , and
- .
Muscle Physiology
When a smooth muscleSmooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
cell is depolarized, it causes opening of the voltage-gated, or L-type, calcium channels. Depolarization may be brought about by stretching of the cell, agonist-binding its G protein-coupled receptor (GPCR), or autonomic nervous system
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
stimulation. Opening of the L-type calcium channel causes influx of extracellular Ca2+, which then binds calmodulin
Calmodulin
Calmodulin is a calcium-binding protein expressed in all eukaryotic cells...
. The activated calmodulin molecule activates myosin light-chain kinase
Myosin light-chain kinase
Myosin light-chain kinase also known as MYLK or MLCK is a serine/threonine-specific protein kinase that phosphorylates the regulatory light chain of myosin II.- Isoforms :Four different MLCK isoforms exist:* MYLK – smooth muscle...
(MLCK), which phosphorylates the myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
in thick filaments. Phosphorylated myosin is able to form crossbridges with actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
thin filaments, and the smooth muscle fiber (i.e., cell) contracts via the sliding filament mechanism
Sliding filament mechanism
The sliding filament theory describes a process used by muscles to contract. It was independently developed by Andrew F. Huxley and Rolf Niedergerke and by Hugh Huxley and Jean Hanson in 1954.-Process of movement:...
. (See reference for an illustration of the signaling cascade involving L-type calcium channels in smooth muscle).
L-type calcium channels are also enriched in the t-tubule
T-tubule
A T-tubule is a deep invagination of the sarcolemma, which is the plasma membrane, only found in skeletal and cardiac muscle cells...
s of striated muscle
Striated muscle
Striated muscle tissue is a form of fibers that are combined into parallel fibers. More specifically, it can refer to:* Cardiac muscle .* Skeletal muscle* Branchiomeric muscles...
cells, i.e., skeletal and cardiac myofibers. When these cells are depolarized, the L-type calcium channels open as in smooth muscle. In skeletal muscle, the actual opening of the channel, which is mechanically gated to a calcium-release channel (a.k.a. ryanodine receptor
Ryanodine receptor
Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons...
, or RYR) in the sarcoplasmic reticulum (SR), causes opening of the RYR. In cardiac muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
, opening of the L-type calcium channel permits influx of calcium into the cell. The calcium binds to the calcium release channels (RYRs) in the SR, opening them; this phenomenon is called "calcium-induced calcium release
Calcium-induced calcium release
Calcium-induced calcium release is a process whereby calcium can trigger release of further calcium from the muscle sarcoplasmic reticulum. Originally proposed for skeletal muscle in the 1970s, subsequent research has revealed that it is even more pronounced in the cardiac muscle...
", or CICR. However the RYRs are opened, either through mechanical-gating or CICR, Ca2+ is released from the SR and is able to bind to troponin C
Troponin C
Troponin C is a part of the troponin complex. It contains four calcium-binding EF hands. It is a component of thin filaments . It contains an N lobe and a C lobe. The C lobe serves a structural purpose and binds to the N domain of TnI. The C lobe can bind either Ca2+ or Mg2+...
on the actin filaments. The muscles then contract through the sliding filament mechanism, causing shortening of sarcomeres and muscle contraction.
See also
- Glutamate receptorGlutamate receptorGlutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
s - Inositol triphosphate receptorInositol triphosphate receptorInositol trisphosphate receptor is a membrane glycoprotein complex acting as Ca2+ channel activated by inositol trisphosphate . InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis,...
- 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...
s - NMDA receptorNMDA receptorThe NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
s - Ryanodine receptorRyanodine receptorRyanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons...
- Voltage-gated ion channelVoltage-gated ion channelVoltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....
s