Cav2.2

Description: calcium channel, voltage-dependent, N type, alpha 1B subunit
Gene: Cacna1b Synonyms: ca2.2, BIII, CACNN, Cav2.2, CACNL1A5, CACNA1B

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Introduction

The N-type calcium channels, also known as a1B or Cav2.2, are high voltage activated (HCA) calcium channels found presynaptically. For a longer introduction, see page 502 in the review [477]. See also the Channelpedia entry for Cav2.1, as this subunit is similar in many respects.

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Gene

GeneID: 257648 Cacna1b calcium channel, voltage-dependent, N type, alpha 1B subunit [ Rattus norvegicus ]

RGD ID	Chromosome	Position	Species
628852	3	2842948-3039747	Rat
735793	2	24461895-24618672	Mouse
1347795	9	140772241-141019076	Human

Cacna1b : calcium channel, voltage-dependent, N type, alpha 1B subunit

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Transcript

Acc No	Sequence	Length	Source
NM_001195199	n/A	n/A	NCBI
NM_147141	n/A	n/A	NCBI
NM_007579	n/A	n/A	NCBI
NM_001042528	n/A	n/A	NCBI
NM_000718	n/A	n/A	NCBI

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Ontology

Accession	Name	Definition	Evidence
GO:0043198	dendritic shaft	Cylindric portion of the dendrite, directly stemming from the perikaryon, and carrying the dendritic spines.	IDA
GO:0005886	plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.	IDA
GO:0043025	neuronal cell body	The portion of a neuron that includes the nucleus, but excludes all cell projections such as axons and dendrites.	IDA
GO:0043679	axon terminus	Terminal inflated portion of the axon, containing the specialized apparatus necessary to release neurotransmitters. The axon terminus is considered to be the whole region of thickening and the terminal button is a specialized region of it.	IDA
GO:0005891	voltage-gated calcium channel complex	A protein complex that forms a transmembrane channel through which calcium ions may pass in response to changes in membrane potential.	IEA
GO:0016021	integral to membrane	Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane.	IEA
GO:0019717	synaptosome	Any of the discrete particles (nerve-ending particles) formed from the clublike presynaptic nerve endings that resist disruption and are snapped or torn off their attachments when brain tissue is homogenized in media isosmotic to plasma.	IDA
GO:0016020	membrane	Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins.	IEA

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Interaction

G proteins

See figure 10 in [94] for the mechanism of G protein modulation in calcium channels and the effect of palmitoylation on the interaction of Cav-beta subunits with the I–II linker.

Neurokinin 1 Receptor

Unlike R-type channels encoded by CaV2.3, L-type (CaV1.3), N- type (CaV2.2), and P/Q-type (CaV2.1) channels are inhibited, but not stimulated, through Neurokinin 1 receptors. [89]

Beta 3 Subunit

Overexpressed beta 3 subunit (12.5 ng/cell cRNA) significantly suppressed N- and R-type, but not L-type calcium channel currents at holding potentials of 60 and 80 mV.[92]

Roscovitine

Roscovitine, a potent inhibitor of cyclin-dependent kinases 1, 2, and 5, slows the deactivation of P/Q (Cav2.1) and N-type (Cav2.2) calcium channels. [93]

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Protein

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Structure

The Cav2.2 subunit consists of four homologous domains (I–IV), each consisting of six trans- membrane (TM) segments. The domains are linked by intracellular loops and have intracellular N and C termini. (see Fig. 1A) in [88]

See also figure 7 in [90] for a structural connection between Cav2.1 and Cav2.2.

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Distribution

presynaptic

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Expression

Cav2.2 can be found in retinal ganglion cells. [259]

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Functional

Cav2.2 control the excitability in retinal ganglion cells and thus are crucial for the development of the visual system. [250]

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Kinetics

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Model

The most detailed model can be found in [250]. It is from hippocampal mossy fiber boutons.

For a Hodgkin Huxley rate equation for the Ca2.2 (= N-type) current, see [260].

Model CaN (ID=6) Edit

Animal	Cat
CellType	RGC
Age	34 Days
Temperature	36.0°C
Reversal	135.0 mV
Ion	Ca +
Ligand ion
Reference	S J Huang et. al; Neuroscience 1998 Jul
mpower	2.0
m Alpha	(0.1*(v-20)/(1-exp(-(v-20)/10))) If v neq 20
m Beta	0.4*exp(-(v+25)/18)
hpower	1.0
h Alpha	0.01*exp(-(v+50)/10)
h Beta	0.1/(1+exp(-(v+17)/17))

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References

Page KM et al. N terminus is key to the dominant negative suppression of Ca(V)2 calcium channels: implications for episodic ataxia type 2.
J. Biol. Chem., 2010 Jan 8 , 285 (835-44).

Meza U et al. Neurokinin 1 receptors trigger overlapping stimulation and inhibition of CaV2.3 (R-type) calcium channels.
Mol. Pharmacol., 2007 Jan , 71 (284-93).

Vitko I et al. Orientation of the calcium channel beta relative to the alpha(1)2.2 subunit is critical for its regulation of channel activity.
PLoS ONE, 2008 , 3 (e3560).

Yasuda T et al. Overexpressed Ca(v)beta3 inhibits N-type (Cav2.2) calcium channel currents through a hyperpolarizing shift of ultra-slow and closed-state inactivation.
J. Gen. Physiol., 2004 Apr , 123 (401-16).

Buraei Z et al. Slowed N-type calcium channel (CaV2.2) deactivation by the cyclin-dependent kinase inhibitor roscovitine.
Biophys. J., 2005 Sep , 89 (1681-91).

Leroy J et al. Interaction via a key tryptophan in the I-II linker of N-type calcium channels is required for beta1 but not for palmitoylated beta2, implicating an additional binding site in the regulation of channel voltage-dependent properties.
J. Neurosci., 2005 Jul 27 , 25 (6984-96).

Helton TD et al. Neuronal L-type calcium channels open quickly and are inhibited slowly.
J. Neurosci., 2005 Nov 2 , 25 (10247-51).

Raghib A et al. Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs.
J. Neurosci., 2001 Nov 1 , 21 (8495-504).

250

Li L et al. Differential gating and recruitment of P/Q-, N-, and R-type Ca2+ channels in hippocampal mossy fiber boutons.
J. Neurosci., 2007 Dec 5 , 27 (13420-9).

259

Huang SJ et al. Activation and inactivation properties of voltage-gated calcium currents in developing cat retinal ganglion cells.
Neuroscience, 1998 Jul , 85 (239-47).

260

Benison G et al. Modeling temporal behavior of postnatal cat retinal ganglion cells.
J. Theor. Biol., 2001 May 21 , 210 (187-99).

477

Catterall WA Structure and regulation of voltage-gated Ca2+ channels.
Annu. Rev. Cell Dev. Biol., 2000 , 16 (521-55).

478

Black JL The voltage-gated calcium channel gamma subunits: a review of the literature.
J. Bioenerg. Biomembr., 2003 Dec , 35 (649-60).

555

Mintz IM et al. Block of calcium channels in rat neurons by synthetic omega-Aga-IVA.
Neuropharmacology, 1993 Nov , 32 (1161-9).

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Credits

Contributors: Rajnish Ranjan, Michael Schartner

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/ionchannels/79/ , accessed on [date]