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 Cav2.2[1] which in humans is encoded by the CACNA1Bgene.[2][3][4]
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]
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.
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^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. PMID16382099.
^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. PMID25296916.
^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. PMID19372737.
^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. PMID12363200.
Mould J, Yasuda T, Schroeder CI, Beedle AM, Doering CJ, Zamponi GW, Adams DJ, Lewis RJ (Aug 2004). "The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels". The Journal of Biological Chemistry. 279 (33): 34705–14. doi:10.1074/jbc.M310848200. PMID15166237.
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Stotz SC, Barr W, McRory JE, Chen L, Jarvis SE, Zamponi GW (Jan 2004). "Several structural domains contribute to the regulation of N-type calcium channel inactivation by the beta 3 subunit". The Journal of Biological Chemistry. 279 (5): 3793–800. doi:10.1074/jbc.M308991200. PMID14602720.
Peng S, Hajela RK, Atchison WD (Dec 2002). "Characteristics of block by Pb2+ of function of human neuronal L-, N-, and R-type Ca2+ channels transiently expressed in human embryonic kidney 293 cells". Molecular Pharmacology. 62 (6): 1418–30. doi:10.1124/mol.62.6.1418. PMID12435810.
Murakami M, Fleischmann B, De Felipe C, Freichel M, Trost C, Ludwig A, Wissenbach U, Schwegler H, Hofmann F, Hescheler J, Flockerzi V, Cavalié A (Oct 2002). "Pain perception in mice lacking the beta3 subunit of voltage-activated calcium channels". The Journal of Biological Chemistry. 277 (43): 40342–51. doi:10.1074/jbc.M203425200. PMID12161429.
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