Calcium channel

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

Contents

• 
  1 Comparison tables
  
  
  
  • 
    1.1 Voltage-gated
    
  
  
  • 
    1.2 Ligand-gated
    
  
  
  
  


• 
  2 Pharmacology
  


• 
  3 References
  


• 
  4 External links
  

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

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)	Cav1.1 (CACNA1S) Cav1.2 (CACNA1C) Cav1.3 (CACNA1D) Cav1.4 (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)	Cav2.1 (CACNA1A)	α2δ, β, possibly γ	Purkinje neurons in the cerebellum / Cerebellar granule cells
N-type calcium channel ("Neural"/"Non-L")	HVA (high-voltage-activated)	Cav2.2 (CACNA1B)	α2δ/β1, β3, β4, possibly γ	Throughout the brain and peripheral nervous system.
R-type calcium channel ("Residual")	intermediate-voltage-activated	Cav2.3 (CACNA1E)	α2δ, β, possibly γ	Cerebellar granule cells, other neurons
T-type calcium channel ("Transient")	low-voltage-activated	Cav3.1 (CACNA1G) Cav3.2 (CACNA1H) Cav3.3 (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

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..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"""""""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
   


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


4. 
   ^ ^abc 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. ISSN 0960-9822. PMID 14680633.
   


7. 
   ^ "The functions of store-operated calcium channels". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1864 (6): 900–906. 2017-06-01. doi:10.1016/j.bbamcr.2016.11.028. ISSN 0167-4889.
   


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.
   

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)

v t e Membrane transport protein: ion channels (TC 1A)
Ca2+: Calcium channel Ligand-gated Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3 Voltage-gated L-type/Cavα 1.1 1.2 1.3 1.4 N-type/Cavα2.2 P-type/Cavα 2.1 Q-type/Cavα2.1 R-type/Cavα2.3 T-type/Cavα 3.1 3.2 3.3 α2δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2
Na+: Sodium channel Constitutively active Epithelial sodium channel α β γ δ Proton-gated Amiloride-sensitive cation channel 1 2 3 4 Voltage-gated Navα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Navβ 1 2 3 4
K+: Potassium channel Calcium-activated BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 KCa 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1 Inward-rectifier KATP Kir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/Kir 3.1 3.2 3.3 3.4 Kir 4.1 4.2 5.1 6.1 6.2 7.1 Tandem pore domain K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18 Voltage-gated Kvα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 Kvα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 Kvβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene
Miscellaneous Cl−: Chloride channel Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B H+: Proton channel HVCN1 M+: CNG cation channel α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4 M+: TRP cation channel TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6 H2O (+ solutes): Porin Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family Cytoplasm: Gap junction Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin
By gating mechanism Ion channel class Ligand-gated Light-gated Voltage-gated Stretch-activated
see also disorders

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