N-type calcium channel

Identifiers

Aliases

External IDs

GeneCards:

Orthologs

Species

Human

Mouse

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View/Edit Human

Illustration of the major elements in a prototypical synapse. Synapses allow nerve cells to communicate with one another through axons and dendrites, converting electrical impulses into chemical signals.

Neuron A (transmitting) to neuron B (receiving)

1. Mitochondrion
2. Synaptic vesicle with neurotransmitters
3. Autoreceptor
4. Synapse with neurotransmitter released (serotonin)
5. Postsynaptic receptors activated by neuro-transmitter (induction of a postsynaptic potential)
6. Calcium channel
7. Exocytosis of a vesicle
8. Recaptured neurotransmitter

The N-type calcium channel is a type of voltage-dependent calcium channel. As with other sub-types of voltage-gated calcium channel, the α₁ subunit forms the pore through which calcium enters the cell and determines most of the channel's properties. The α₁ subunit is also known as the calcium channel, voltage-dependent, N type, alpha 1B subunit (CACNA1B) or Ca_v2.2^[1] which in humans is encoded by the CACNA1B gene.^[2]^[3]^[4]

Clinical significance

Mutations in CACNA1B are associated to Myoclonus-Dystonia syndrome .^[5]

Structure

In addition to the α₁ subunit, the following subunits are present in the N-type calcium channel:

α₂δ – CACNA2D1, CACNA2D2
β₁ – CACNB1
β₃ – CACNB3
β₄ – CACNB4

Function

N-type ('N' for "Neural-Type" ) calcium channels are found primarily at presynaptic terminals and are involved in neurotransmission.^[6] Strong depolarization by an action potential causes these channels to open and allow influx of Ca²⁺, initiating vesicle fusion and release of stored neurotransmitter. N-type channels are blocked by ω-conotoxin.^[1]

Therapeutic Potential

Blockade of the N-type calcium channel is a potential therapeutic strategy for the treatment of alcoholism.^[7]^[8] Blockade of N-type calcium channels in sensory neurons has therapeutic potential for the treatment of certain types of pain, particularly neuropathic pain. The peptide N-type calcium channel blocker ziconotide is given intrathecally for intractable pain.

Blockers

References

1 2 Williams ME, Brust PF, Feldman DH, Patthi S, Simerson S, Maroufi A, McCue AF, Veliçelebi G, Ellis SB, Harpold MM (Jul 1992). "Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel". Science. 257 (5068): 389–95. Bibcode:1992Sci...257..389W. doi:10.1126/science.1321501. PMID 1321501.
↑ "Entrez Gene: CACNA1B calcium channel, voltage-dependent, N type, alpha 1B subunit".
↑ Diriong S, Lory P, Williams ME, Ellis SB, Harpold MM, Taviaux S (Dec 1995). "Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits". Genomics. 30 (3): 605–9. doi:10.1006/geno.1995.1284. PMID 8825650.
↑ Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (Dec 2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacological Reviews. 57 (4): 411–25. doi:10.1124/pr.57.4.5. PMID 16382099.
↑ Groen JL, Andrade A, Ritz K, Jalalzadeh H, Haagmans M, Bradley TE, Jongejan A, Verbeek DS, Nürnberg P, Denome S, Hennekam RC, Lipscombe D, Baas F, Tijssen MA (Feb 2015). "CACNA1B mutation is linked to unique myoclonus-dystonia syndrome". Human Molecular Genetics. 24 (4): 987–93. doi:10.1093/hmg/ddu513. PMID 25296916.
↑ Kurihara T, Tanabe T (Apr 2003). "N-type Ca2+ channel". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica. 121 (4): 211–22. doi:10.1254/fpj.121.211. PMID 12777840.
1 2 Newton PM, Zeng L, Wang V, Connolly J, Wallace MJ, Kim C, Shin HS, Belardetti F, Snutch TP, Messing RO (Nov 2008). "A blocker of N- and T-type voltage-gated calcium channels attenuates ethanol-induced intoxication, place preference, self-administration, and reinstatement". The Journal of Neuroscience. 28 (45): 11712–9. doi:10.1523/JNEUROSCI.3621-08.2008. PMC 3045811. PMID 18987207. Lay summary – Psychology Today.
↑ Newton PM, Messing RO (2009). "The N-type calcium channel is a novel target for treating alcohol use disorders". Channels. 3 (2): 77–81. doi:10.4161/chan.3.2.8037. PMID 19372737.
↑ Vega-Hernández A, Felix R (Apr 2002). "Down-regulation of N-type voltage-activated Ca2+ channels by gabapentin". Cellular and Molecular Neurobiology. 22 (2): 185–90. PMID 12363200.
↑ Lukyanetz EA, Shkryl VM, Kostyuk PG (Jan 2002). "Selective blockade of N-type calcium channels by levetiracetam". Epilepsia. 43 (1): 9–18. doi:10.1046/j.1528-1157.2002.24501.x. PMID 11879381.
↑ Wang SJ, Huang CC, Hsu KS, Tsai JJ, Gean PW (Nov 1996). "Inhibition of N-type calcium currents by lamotrigine in rat amygdalar neurones". NeuroReport. 7 (18): 3037–40. doi:10.1097/00001756-199611250-00048. PMID 9116235.
↑ Li SN, Bräter M, Andreas K (Feb 1999). "Nicardipine inhibits N-type calcium channels in dbcAMP-differentiated neuroblastoma x glioma hybrid cells (NG 108-15 cells)". Acta Pharmacologica Sinica. 20 (2): 117–120. PMID 10437156.

External links

CACNA1B protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
N-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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