Calcium channel

A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel,[1] although there are also ligand-gated calcium channels.[2]

Comparison tables

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

Voltage-gated

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
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
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.
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

the receptor-operated calcium channels (in vasoconstriction)
- P2X receptors[3]

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]
Cation channels of sperm	Calcium (CICR)	PKD2 family	sperm (specifically flagella)	non-selective calcium-activated cation channel directing sperm in female reproductive tract[6]
store-operated channels	indirectly by ER/SR depletion of calcium[4]	ORAI1, ORAI2, ORAI3	plasma membrane	provide calcium signaling to the cytoplasm[7]

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.[8]

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.[9]

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): 490–5. doi:10.1016/S0955-0674(96)80025-1. PMID 8791458.
Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 479
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.
Gao, Zhiqian; Ruden, Douglas M.; Lu, Xiangyi (2003-12-16). "PKD2 cation channel is required for directional sperm movement and male fertility". Current Biology. 13 (24): 2175–2178. doi:10.1016/j.cub.2003.11.053. ISSN 0960-9822. PMID 14680633.
Putney, James W.; Steinckwich-Besançon, Natacha; Numaga-Tomita, Takuro; Davis, Felicity M.; Desai, Pooja N.; d'Agostin, Diane M.; Wu, Shilan; Bird, Gary S. (2017-06-01). "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. ISSN 0167-4889. PMC 5420336. PMID 27913208.
Katz, A. M. (September 1986). "Pharmacology and mechanisms of action of calcium-channel blockers". Journal of Clinical Hypertension. 2 (3 Suppl): 28S–37S. ISSN 0748-450X. PMID 3540226.
Zamponi, Gerald W.; Lory, Philippe; Perez-Reyes, Edward (July 2010). "Role of voltage-gated calcium channels in epilepsy". Pflügers Archiv. 460 (2): 395–403. doi:10.1007/s00424-009-0772-x. ISSN 0031-6768. PMC 3312315. PMID 20091047.

External links

"Voltage-Gated Ion Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
"TRIP Database". a manually curated database of protein-protein interactions for mammalian TRP channels.
Calcium+Channels at the US National Library of Medicine Medical Subject Headings (MeSH)

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[1] "calcium channel" at Dorland's Medical Dictionary

[pmid8791458-2] Striggow F, Ehrlich BE (August 1996). "Ligand-gated calcium channels inside and out". Current Opinion in Cell Biology. 8 (4): 490–5. doi:10.1016/S0955-0674(96)80025-1. PMID 8791458.

[boron-3] Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 479

[Rang53-4] Rang HP (2003). Pharmacology. Edinburgh: Churchill Livingstone. p. 54. ISBN 978-0-443-07145-4.

[5] "TPCN1 - Two pore calcium channel protein 1 - Homo sapiens (Human) - TPCN1 gene & protein". www.uniprot.org. Retrieved 2017-12-11.

[6] Gao, Zhiqian; Ruden, Douglas M.; Lu, Xiangyi (2003-12-16). "PKD2 cation channel is required for directional sperm movement and male fertility". Current Biology. 13 (24): 2175–2178. doi:10.1016/j.cub.2003.11.053. ISSN 0960-9822. PMID 14680633.

[7] Putney, James W.; Steinckwich-Besançon, Natacha; Numaga-Tomita, Takuro; Davis, Felicity M.; Desai, Pooja N.; d'Agostin, Diane M.; Wu, Shilan; Bird, Gary S. (2017-06-01). "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. ISSN 0167-4889. PMC 5420336. PMID 27913208.

[8] Katz, A. M. (September 1986). "Pharmacology and mechanisms of action of calcium-channel blockers". Journal of Clinical Hypertension. 2 (3 Suppl): 28S–37S. ISSN 0748-450X. PMID 3540226.

[9] Zamponi, Gerald W.; Lory, Philippe; Perez-Reyes, Edward (July 2010). "Role of voltage-gated calcium channels in epilepsy". Pflügers Archiv. 460 (2): 395–403. doi:10.1007/s00424-009-0772-x. ISSN 0031-6768. PMC 3312315. PMID 20091047.