Calcium channel

{{Short description|Ion channel complex through which calcium ions pass}}

A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel,{{DorlandsDict|two/000019812|calcium channel}} which are a type of calcium channel regulated by changes in membrane potential. Some calcium channels are regulated by the binding of a ligand.Striggow F, Ehrlich BE (August 1996). "Ligand-gated calcium channels inside and out". Current Opinion in Cell Biology. 8 (4): 490–495. doi:10.1016/S0955-0674(96)80025-1. PMID [https://pubmed.ncbi.nlm.nih.gov/8791458/ 8791458].{{Cite journal |last=Zamponi |first=Gerald W. |date=2017-12-20 |title=A Crash Course in Calcium Channels |journal=ACS Chemical Neuroscience |language=en |volume=8 |issue=12 |pages=2583–2585 |doi=10.1021/acschemneuro.7b00415 |pmid=29131938 |issn=1948-7193|doi-access=free }} 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.

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=

{{Main|voltage-gated calcium channel}}

  • voltage-operated calcium channels

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| Type

Voltageα1 subunit (gene name)Associated subunitsMost often found in
L-type calcium channel ("Long-Lasting" AKA "DHP Receptor")HVA (high voltage activated)Cav1.1 ({{Gene|CACNA1S}})
Cav1.2 ({{Gene|CACNA1C}}) Cav1.3 ({{Gene|CACNA1D}})
Cav1.4 ({{Gene|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 ({{Gene|CACNA1B}})α2δ/β1, β3, β4, possibly γThroughout the brain and peripheral nervous system.
P-type calcium channel ("Purkinje") /Q-type calcium channelHVA (high voltage activated)Cav2.1 ({{Gene|CACNA1A}})α2δ, β, possibly γPurkinje neurons in the cerebellum / Cerebellar granule cells
R-type calcium channel ("Residual")intermediate-voltage-activatedCav2.3 ({{Gene|CACNA1E}})α2δ, β, possibly γCerebellar granule cells, other neurons
T-type calcium channel ("Transient")low-voltage-activatedCav3.1 ({{Gene|CACNA1G}})
Cav3.2 ({{Gene|CACNA1H}})
Cav3.3 ({{Gene|CACNA1I}})
neurons, cells that have pacemaker activity, bone (osteocytes), thalamus (thalamus)

=Ligand-gated=

  • receptor-operated calcium channels

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| Type

Gated byGeneLocationFunction
IP3 receptorIP3ITPR1, ITPR2, ITPR3ER/SRReleases calcium from ER/SR in response to IP3 by e.g. GPCRs{{cite book | vauthors = Rang HP |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |isbn=978-0-443-07145-4 |page = 54 }}
Ryanodine receptordihydropyridine receptors in T-tubules and increased intracellular calcium (Calcium Induced Calcium Release - CICR)RYR1, RYR2, RYR3ER/SRCalcium-induced calcium release in myocytes
Two-pore channelNicotinic acid adenine dinucleotide phosphate (NAADP)TPCN1, TPCN2endosomal/lysosomal membranesNAADP-activated calcium transport across endosomal/lysosomal membranes{{Cite web|url=https://www.uniprot.org/uniprot/Q9ULQ1|title=TPCN1 - Two pore calcium channel protein 1 - Homo sapiens (Human) - TPCN1 gene & protein|website=www.uniprot.org|language=en|access-date=2017-12-11}}
store-operated channels{{Cite journal |last1=Prakriya |first1=Murali |last2=Lewis |first2=Richard S. |date=Oct 2015 |title=Store-Operated Calcium Channels |journal=Physiological Reviews |language=en |volume=95 |issue=4 |pages=1383–1436 |doi=10.1152/physrev.00020.2014 |issn=0031-9333 |pmc=4600950 |pmid=26400989}}indirectly by ER/SR depletion of calciumORAI1, ORAI2, ORAI3plasma membraneProvides calcium signaling to the cytoplasm{{cite journal | vauthors = Putney JW, Steinckwich-Besançon N, Numaga-Tomita T, Davis FM, Desai PN, D'Agostin DM, Wu S, Bird GS | display-authors = 6 | title = The functions of store-operated calcium channels | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research| volume = 1864 | issue = 6 | pages = 900–906 | date = June 2017 | pmid = 27913208 | pmc = 5420336 | doi = 10.1016/j.bbamcr.2016.11.028 }}

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.{{Cite book |last1=Zheng |first1=Jie |url=https://www.taylorfrancis.com/books/9781003096276 |title=Textbook of Ion Channels Volume II: Properties, Function, and Pharmacology of the Superfamilies |last2=Trudeau |first2=Matthew C. |date=2023-06-06 |publisher=CRC Press |isbn=978-1-003-09627-6 |edition=1 |location=Boca Raton |language=en |doi=10.1201/9781003096276|s2cid=259784278 }} 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.{{Cite journal |last1=Wu |first1=Jianping |last2=Yan |first2=Zhen |last3=Li |first3=Zhangqiang |last4=Yan |first4=Chuangye |last5=Lu |first5=Shan |last6=Dong |first6=Mengqiu |last7=Yan |first7=Nieng |date=2015-12-18 |title=Structure of the voltage-gated calcium channel Ca v 1.1 complex |url=https://www.science.org/doi/10.1126/science.aad2395 |journal=Science |language=en |volume=350 |issue=6267 |pages=aad2395 |doi=10.1126/science.aad2395 |pmid=26680202 |s2cid=22271779 |issn=0036-8075|url-access=subscription }}

Pharmacology

File:L-type_calcium_channel.jpg

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.{{cite journal | vauthors = Katz AM | title = Pharmacology and mechanisms of action of calcium-channel blockers | journal = Journal of Clinical Hypertension | volume = 2 | issue = 3 Suppl | pages = 28S–37S | date = September 1986 | pmid = 3540226 }}

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.{{cite journal | vauthors = Zamponi GW, Lory P, Perez-Reyes E | title = Role of voltage-gated calcium channels in epilepsy | journal = Pflügers Archiv | volume = 460 | issue = 2 | pages = 395–403 | date = July 2010 | pmid = 20091047 | pmc = 3312315 | doi = 10.1007/s00424-009-0772-x }}

See also

  • {{annotated link|Calcium in biology}}.

References

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