Illustration of the major elements in a prototypical synapse. Synapses allow nerve cells to communicate with one another through axons and dendrites, converting electrical impulses into chemical signals.

Neuron A (transmitting) to neuron B (receiving)
1. Mitochondria
2. synaptic vesicle with neurotransmitters
3. Autoreceptor
4. synapse with neurotransmitter released (serotonin)
5. postsynaptic receptors activated by neuro-transmitter (induction of a postsynaptic potential)
6. calcium channel
7. Exocytosis of a vesicle
8. Recaptured neurotransmitter

Voltage-dependent calcium channels (VDCC) are a group of voltage-gated ion channels found in excitable cells (neurons, glial cells, muscle cells, etc.) with a permeability to the ion Ca²⁺, which plays a role in the membrane potential. VDCCs are involved in the release of neurotransmitters and hormones, muscular contraction, excitability of neurons and gene expression. Image File history File links Download high-resolution version (859x564, 69 KB)I created this image. ... Image File history File links Download high-resolution version (859x564, 69 KB)I created this image. ... Illustration of the major elements in a prototypical synapse. ... Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. ... An axon, or nerve fiber, is a long slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neurons cell body or soma. ... The term Dendrite stems from the Greek word dendron (literally “tree”), and typically refers to the branched projections of a neuron that act to conduct the electrical stimulation received from other cells to and from the cell body, or soma of the neuron from which the dendrites project. ... A. A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a cell membrane. ... Chemical structure of D-Aspartic Acid, a common Amino Acid neurotransmitter. ... Voltage-gated ion channel is a ion channel that is specifically activated, or gated, by the surrounding potential difference near the channel (or near the cell, neuron or synapse). ... Ion channels are pore-forming proteins that help to establish and control the small voltage gradient that exists across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient. ... Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. ... This article or section does not cite its references or sources. ... General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Atomic mass 40. ... This article or section is in need of attention from an expert on the subject. ... Chemical structure of D-Aspartic Acid, a common Amino Acid neurotransmitter. ... A hormone (from Greek horman - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... It has been suggested that this article or section be merged into Muscular system. ... Gene expression, or simply expression, is the process by which a genes DNA sequence is converted into the structures and functions of a cell. ...

Types of VDCC

Calcium channel blockers are a class of drugs with effects on the muscle of the heart and the muscles of the rest of the body. ... Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress fast rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation. ... In medicine and pharmacology, antihypertensives are a class of drugs that are used in the treatment of arterial hypertension. ... The heart and lungs, from an older edition of Grays Anatomy. ... Nifedipine (brand name Adalat and Procardia) is a dihydropyridine calcium channel blocker. ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain and to achieve analgesia. ... Ziconotide is a non-opioid, non local anesthetic used for the amelioration of chronic pain. ... The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. ...

Structure

Voltage-dependent calcium channels are formed as a complex of several different subunits: α1, α2, β, γ, and δ. The α1 subunit is the one that determines most of the channel's properties.

High voltage gated calcium channels

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High voltage gated calcium channels (HVGCCs) are structurally homologous among varying types and are differentiated according to their physiological roles and/or inhibition by specific toxins. High voltage gated calcium channels include the neural N-type channel blocked by ω-conotoxins, the residual R-type channel involved in processes in the brain and muscle, 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. The venom of the black widow spider is a potent latrotoxin. ... Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. ... A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail. ... In animals, the brain, or encephalon (Greek for in the head), is the control center of the central nervous system. ... It has been suggested that this article or section be merged into Muscular system. ... A top-down view of skeletal muscle Skeletal muscle is a type of striated muscle, attached to the skeleton. ... Smooth muscle of the aorta. ... Cardiac muscle is a type of involuntary mononucleated, or uninucleated, striated muscle found exclusively within the heart. ...

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. There are multiple α 1 subunits that have been classified.

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: CACNB1, CACNB2, CACNB3, and CACNB4.

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.^[1] Therefore the β subunit functions initially to regulate the current density by controlling the amount of α 1 subunit expressed at the cell membrane. The endoplasmic reticulum (endoplasmic meaning within the cytoplasm, reticulum meaning little net in Latin) or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport (e. ...

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 depolarizations. The β subunit has effects on the kinetics of the cardiac α1C in Xenopus oocytes co-expressed with β subunits. The β subunit acts as an important modulator of channel electrophysiological properties. In biology, depolarization is the event a cell undergoes when its membrane potential grows more positive with respect to the extracellular solution. ... Species Xenopus amieti (volcano clawed frog) Xenopus andrei (Andres clawed frog) Xenopus borealis (Kenyan clawed frog) Xenopus boumbaensis (Mawa clawed frog) Xenopus clivii (Eritrea clawed frog) Xenopus fraseri (Frasers clawed frog) Xenopus gilli (Cape clawed frog) Xenopus laevis (African clawed frog) Xenopus largeni Xenopus longipes (savannah clawed frog...

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. The general structure of an α-amino acid molecule, with the amine group on the left and the carboxyl group on the right. ...

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: CACNA2D1, CACNA2D2, CACNA2D3, CACNA2D4.

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. Gabapentin (brand name: Neurontin®) was initially synthesized to mimic the structure of GABA for the treatment of epilepsy. ... Pregabalin (brand name: Lyrica®) is a new anticonvulsant drug indicated as an add on therapy for partial onset seizures and for certain types of neuropathic pain. ...

γ subunit

The γ subunit is associated with only some of the HVGCC complexes. The γ subunit glycoprotein (33 kDa) is composed of four transmembrane spanning helices. The γ subunits does not affect trafficking and for the most part is not required to regulate the channel complex. The γ1 subunit is associated with skeletal muscle while the γ2 and γ3 may be associated with the P/Q and N-type channels. However, γ2, γ3, γ4 and γ8 are also associated with AMPA glutamate receptors.

There are 8 genes for the gamma subunit: CACNG1, CACNG2, CACNG3, CACNG4, CACNG5, CACNG6, CACNG7, and CACNG8.

See also

• Ion channels
• Voltage-gated ion channels
• Glutamate receptors
• NMDA receptors
• Ryanodine receptor

Ion channels are pore-forming proteins that help to establish and control the small voltage gradient that exists across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient. ... Voltage-gated ion channel is a ion channel that is specifically activated, or gated, by the surrounding potential difference near the channel (or near the cell, neuron or synapse). ... Glutamate is a neurotransmitter in nerve cells which binds to all glutamate receptors located on neuron membranes, and is an example of a transmembrane receptor. ... The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate (NMDA (N-methyl d-aspartate) is a name of its selective specific agonist). ... Ryanodine receptors form a class of calcium channels in various forms of muscle. ...

External links

• Ion Channels at cf.ac.uk
• MeSH Calcium+Channels

Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ...

References

• Calcium channels - basic aspects of their structure, function and gene encoding; anesthetic action on the channels - a review. Canadian Journal of Anesthesia, 49:151-164 (2002).
• 1. ^ Bichet D, Cornet V, Geib S, Carlier E, Volsen S, Hoshi T, Mori Y, De Waard M (2000). "The I-II loop of the Ca2+ channel α 1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit.". Neuron 25 (1): 177-90. PMID 10707982.