L-type calcium channel

See also: Cardiac action potential

Calcium channel, voltage-dependent
Crystallographic structure
Identifiers
Symbol	Calcium channel, voltage-dependent

Immunohistochemical analysis of L-type calcium channel Cav1.3 (CACNA1D) in human adrenal cortex. Marked immunoreactivity was detected in the zona glomerulosa. In the figure: ZG = zona glomerulosa, ZF = zona fasciculata, AC = adrenal capsule. Immunohistochemistry was performed according to published methods.^[1]

The L-type calcium channel (also known as the dihydropyridine channel, or DHP channel) is part of the high-voltage activated family of voltage-dependent calcium channel.^[2] "L" stands for long-lasting referring to the length of activation. This channel has four subunits (Cav1.1, Cav1.2, Cav1.3, Cav1.4).

L-type calcium channels are responsible for the excitation-contraction coupling of skeletal, smooth, cardiac muscle, and for aldosterone secretion in endocrine cells of the adrenal cortex.^[1]

In cardiac myocytes, the L-type calcium channel passes inward Ca²⁺ current and triggers calcium release from the sarcoplasmic reticulum by activating ryanodine receptor 2 (RyR2) (calcium-induced-calcium-release).^[3] Phosphorylation of these channels increases their permeability to calcium and increases the contractility of their respective cardiac myocytes.

L-type calcium channel blocker drugs are used as cardiac antiarrhythmics or antihypertensives, depending on whether the drugs have higher affinity for the heart (the phenylalkylamines, like verapamil), or for the vessels (the dihydropyridines, like nifedipine).

In skeletal muscle, there is a very high concentration of L-type calcium channels, situated in the T-tubules. Muscle depolarization results in large gating currents, but anomalously low calcium flux, which is now explained by the very slow activation of the ionic currents. For this reason, little or no Ca²⁺ passes across the T-tubule membrane during a single action potential.

Structure

Like most voltage-gated ion channels, the α-subunit is composed of 4 subunits. Each subunit is formed by 6 alpha-helical, transmembrane domains that cross the membrane (numbered S1-S6). The S1-S4 subunits make up the voltage sensor, while S5-S6 subunits make up the selectivity filter.^[4]

Alpha subunit of a generic voltage-gated ion channel

Genes

CACNA1C, CACNA1D, CACNA1S, CACNA1F

References

1 2 Felizola SJ, Maekawa T, Nakamura Y, Satoh F, Ono Y, Kikuchi K, Aritomi S, Ikeda K, Yoshimura M, Tojo K, Sasano H (2014). "Voltage-gated calcium channels in the human adrenal and primary aldosteronism.". J Steroid Biochem Mol Biol. 144 (part B): 410–416. doi:10.1016/j.jsbmb.2014.08.012. PMID 25151951.
↑ Rossier, Michel F. (2016). "T-Type Calcium Channel: A Privileged Gate for Calcium Entry and Control of Adrenal Steroidogenesis". Frontiers in Endocrinology. 7. doi:10.3389/fendo.2016.00043. ISSN 1664-2392.
↑ Yamakage M, Namiki A (2002). "Calcium channels — basic aspects of their structure, function and gene encoding; anesthetic action on the channels — a review". Can J Anaesth 49 (2): 151–64. doi:10.1007/BF03020488. PMID 11823393.
↑ Catterall, William A.; Perez-Reyes, Edward; Snutch, Terrance P.; Striessnig, Joerg (December 2005). "International Union of Pharmacology. XLVIII. Nomenclature and Structure-Function Relationships of Voltage-Gated Calcium Channels". Pharmacol Rev. 57 (4): 411–425. doi:10.1124/pr.57.4.5. PMID 16382099. Retrieved 30 November 2014.

External links

"Voltage-Gated Calcium Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
L-Type Calcium Channel at the US National Library of Medicine Medical Subject Headings (MeSH)

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/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 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	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 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	K_vα1-6 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 K_vα7-12 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 K_vβ 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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