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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.

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

voltage-operated calcium channels

Type	Voltage	α₁ subunit (gene name)	Associated subunits	Most often found in
L-type calcium channel ("Long-Lasting" AKA "DHP Receptor")	HVA (high voltage activated)	Ca_v1.1 (CACNA1S) Ca_v1.2 (CACNA1C) Ca_v1.3 (CACNA1D) Ca_v1.4 (CACNA1F)	α₂δ, β, γ	Skeletal 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)	Ca_v2.2 (CACNA1B)	α₂δ/β₁, β₃, β₄, possibly γ	Throughout the brain and peripheral nervous system.
P-type calcium channel ("Purkinje") /Q-type calcium channel	HVA (high voltage activated)	Ca_v2.1 (CACNA1A)	α₂δ, β, possibly γ	Purkinje neurons in the cerebellum / Cerebellar granule cells
R-type calcium channel ("Residual")	intermediate-voltage-activated	Ca_v2.3 (CACNA1E)	α₂δ, β, possibly γ	Cerebellar granule cells, other neurons
T-type calcium channel ("Transient")	low-voltage-activated	Ca_v3.1 (CACNA1G) Ca_v3.2 (CACNA1H) Ca_v3.3 (CACNA1I)		neurons, cells that have pacemaker activity, bone (osteocytes), thalamus (thalamus)

Ligand-gated

receptor-operated calcium channels

Type	Gated by	Gene	Location	Function
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, TPCN2	endosomal/lysosomal membranes	NAADP-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 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]

References

^ "calcium channel" at Dorland's Medical Dictionary
^ 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 8791458.
^ Zamponi, Gerald W. (2017-12-20). "A Crash Course in Calcium Channels". ACS Chemical Neuroscience. 8 (12): 2583–2585. doi:10.1021/acschemneuro.7b00415. ISSN 1948-7193. PMID 29131938.
^ ^a ^b ^c Rang HP (2003). Pharmacology. Edinburgh: Churchill Livingstone. p. 54. ISBN 978-0-443-07145-4.
^ "TPCN1 - Two pore calcium channel protein 1 - Homo sapiens (Human) - TPCN1 gene & protein". www.uniprot.org. Retrieved 2017-12-11.
^ Prakriya, Murali; Lewis, Richard S. (Oct 2015). "Store-Operated Calcium Channels". Physiological Reviews. 95 (4): 1383–1436. doi:10.1152/physrev.00020.2014. ISSN 0031-9333. PMC 4600950. PMID 26400989.
^ Putney JW, Steinckwich-Besançon N, Numaga-Tomita T, Davis FM, Desai PN, D'Agostin DM, et al. (June 2017). "The functions of store-operated calcium channels". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1864 (6): 900–906. doi:10.1016/j.bbamcr.2016.11.028. PMC 5420336. PMID 27913208.
^ Zheng, Jie; Trudeau, Matthew C. (2023-06-06). Textbook of Ion Channels Volume II: Properties, Function, and Pharmacology of the Superfamilies (1 ed.). Boca Raton: CRC Press. doi:10.1201/9781003096276. ISBN 978-1-003-09627-6. S2CID 259784278.
^ Wu, Jianping; Yan, Zhen; Li, Zhangqiang; Yan, Chuangye; Lu, Shan; Dong, Mengqiu; Yan, Nieng (2015-12-18). "Structure of the voltage-gated calcium channel Ca v 1.1 complex". Science. 350 (6267): aad2395. doi:10.1126/science.aad2395. ISSN 0036-8075. PMID 26680202. S2CID 22271779.
^ Katz AM (September 1986). "Pharmacology and mechanisms of action of calcium-channel blockers". Journal of Clinical Hypertension. 2 (3 Suppl): 28S–37S. PMID 3540226.
^ Zamponi GW, Lory P, Perez-Reyes E (July 2010). "Role of voltage-gated calcium channels in epilepsy". Pflügers Archiv. 460 (2): 395–403. doi:10.1007/s00424-009-0772-x. PMC 3312315. PMID 20091047.

External links

"The Weiss Lab". The Weiss Lab is investigating the molecular and cellular mechanisms underlying human diseases caused by dysfunction of ion channels.
"Voltage-Gated Ion Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2021-04-17. Retrieved 2008-12-17.
"TRIP Database". a manually curated database of protein-protein interactions for mammalian TRP channels. Archived from the original on 2016-08-10. Retrieved 2021-06-18.
Calcium+Channels at the U.S. National Library of Medicine Medical Subject Headings (MeSH)