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
Main article: voltage-gated calcium channel
TypeVoltageα1 subunit (gene name)Associated subunitsMost often found in
L-type calcium channel ("Long-Lasting" AKA "DHP Receptor")HVA (high voltage activated)Cav1.1 (CACNA1S)
Cav1.2 (CACNA1C) Cav1.3 (CACNA1D)
Cav1.4 (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
P-type calcium channel ("Purkinje") /Q-type calcium channelHVA (high voltage activated)Cav2.1 (CACNA1A)α2δ, β, possibly γPurkinje neurons in the cerebellum / Cerebellar granule cells
N-type calcium channel ("Neural"/"Non-L")HVA (high-voltage-activated)Cav2.2 (CACNA1B)α2δ/β1, β3, β4, possibly γThroughout the brain and peripheral nervous system.
R-type calcium channel ("Residual")intermediate-voltage-activatedCav2.3 (CACNA1E)α2δ, β, possibly γCerebellar granule cells, other neurons
T-type calcium channel ("Transient")low-voltage-activatedCav3.1 (CACNA1G)
Cav3.2 (CACNA1H)
Cav3.3 (CACNA1I)		neurons, cells that have pacemaker activity, bone (osteocytes), thalamus (thalamus)

Ligand-gated
TypeGated byGeneLocationFunction
IP3 receptorIP3ITPR1, ITPR2, ITPR3ER/SRReleases calcium from ER/SR in response to IP3 by e.g. GPCRs[4]
Ryanodine receptordihydropyridine receptors in T-tubules and increased intracellular calcium (Calcium Induced Calcium Release - CICR)RYR1, RYR2, RYR3ER/SRCalcium-induced calcium release in myocytes[4]
Two-pore channelNicotinic Acid Adenine Dinucleotide Phosphate (NAADP)TPCN1, TPCN2endosomal/lysosomal membranesNAADP-activated calcium transport across endosomal/lysosomal membranes[5]
Cation channels of spermCalcium (CICR) PKD2 family sperm (specifically flagella) non-selective calcium-activated cation channel directing sperm in female reproductive tract[6]
store-operated channelsindirectly by ER/SR depletion of calcium[4]ORAI1, ORAI2, ORAI3plasma membraneprovide 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
  1. "calcium channel" at Dorland's Medical Dictionary
  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.
  3. Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 479
  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.
  • "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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