Channelpedia

Cav2.3

Description: calcium channel, voltage-dependent, R type, alpha 1E subunit
Gene: Cacna1e     Synonyms: cacna1e, cav2.3, ca2.3

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Introduction

The R type calcium channel, also know as a1E or Cav2.3, is an HVA calcium channel found in neurons. R-type Ca2+ currents have been pharmacologically defined by their resistance to blockers of L-type, N-type, and P/Q-type Ca2+ channels [512] and by their sensitivity to SNX-482, a peptide component of spider venom [513].


Experimental data


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Gene

GeneID: 54234 Cacna1e calcium channel, voltage-dependent, R type, alpha 1E subunit [ Rattus norvegicus ]

RGD ID Chromosome Position Species
2246 13 69367254-69683943 Rat
733703 1 156239649-156573050 Mouse
733702 1 181452716-181770716 Human

Cacna1e : calcium channel, voltage-dependent, R type, alpha 1E subunit


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Transcript

Acc No Sequence Length Source
NM_019294 n/A n/A NCBI
NM_009782 n/A n/A NCBI
NM_000721 n/A n/A NCBI

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Ontology

Accession Name Definition Evidence
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. TAS
GO:0043204 perikaryon The portion of the cell soma (cell body) that excludes the nucleus. 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-alpha-q/11-coupled Muscarinic Acetylcholine

Cav2.3 is both inhibited and stimulated through G-alpha-q/11-coupled muscarinic acetylcholine receptors [526], [89].

Interaction with alpha1C channel

A chimeric channel containing the I-II linker from alpha1E (Cav2.3) accelerated the inactivation kinetics of alpha1C [527].

Mibefradil

Mibefradil (RO 40-5967), which has been used clinically as an anti-hypertensive and antianginal agent is modulating Ca2.3's inactivation kinetics. [100]


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Protein


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Structure

Point mutationins R387E in alpha1E channels significantly influence both the kinetics and the voltage dependence of inactivation. [97]

Altogether our findings identify S6 hydrophobic residues in Domains I to IV that play a unique role in controlling the relative stability of the open and closes states in CaV2.3. [99]


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Distribution

Cav2.3 channels are located in dendritic spines. [518]


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Expression


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Functional

Cav2.3 is involved in cerebellar function, morphine tolerance, and synaptic plasticity [519], [520], [521], [522], [523]. It is noteworthy that CaV2.3 is also implicated in nociception, as evidenced by the fact that CaV2.3 knockout mice exhibit functional deficits in pain per- ception [524] and intrathecal injection of SNX-482 produces analgesia [525].


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Kinetics

R-type currents - mediated by Cav2.3 channels - participate in neurosecretion and in the formation of afterdepolarizations, plateau potentials, and bursting activity in hippocampal CA1 pyramidal neurons [514], [515], [516], [517].


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Model

[1] Ca_R (Model ID = 7)

Animalrat
CellType Cerebellar
Age 21 Days
Temperature36.0°C
Reversal 135.0 mV
Ion Ca +
Ligand ion
Reference T Miyasho et. al; Brain Res. 2001 Feb 9
mpower 1.0
mAlpha 2.6/(1+exp((v+7)/-8))
mBeta 0.18/(1+exp((v+26)/4))
hpower 1.0
hAlpha 0.0025/(1+exp((v+32)/8))
hBeta 0.19/(1+exp((v+42)/-10))
46

MOD - xml - channelML


References

99

Raybaud A. et al. The role of distal S6 hydrophobic residues in the voltage-dependent gating of CaV2.3 channels.
J. Biol. Chem., 2007 Sep 21 , 282 (27944-52).

100

Bernatchez G. et al. State-dependent inhibition of inactivation-deficient Ca(V)1.2 and Ca(V)2.3 channels by mibefradil.
J. Membr. Biol., 2001 Nov 15 , 184 (143-59).

340

Randall AD. et al. Contrasting biophysical and pharmacological properties of T-type and R-type calcium channels.
Neuropharmacology, 1997 Jul , 36 (879-93).

514

Wu L. et al. Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2.
Nature, 2002 Oct 31 , 419 (947-52).

517

Macvicar BA. et al. Muscarinic enhancement of R-type calcium currents in hippocampal CA1 pyramidal neurons.
J. Neurosci., 2006 Jun 7 , 26 (6249-58).

518

Sabatini BL. et al. Analysis of calcium channels in single spines using optical fluctuation analysis.
Nature, 2000 Nov 30 , 408 (589-93).

519

Tanabe T. et al. Intact LTP and fear memory but impaired spatial memory in mice lacking Ca(v)2.3 (alpha(IE)) channel.
Biochem. Biophys. Res. Commun., 2001 Mar 23 , 282 (242-8).

520

Breustedt J. et al. Alpha1E-containing Ca2+ channels are involved in synaptic plasticity.
Proc. Natl. Acad. Sci. U.S.A., 2003 Oct 14 , 100 (12450-5).

521

Beck H. et al. Functional specialization of presynaptic Cav2.3 Ca2+ channels.
Neuron, 2003 Jul 31 , 39 (483-96).

523

Saegusa H. et al. Altered cerebellar function in mice lacking CaV2.3 Ca2+ channel.
Biochem. Biophys. Res. Commun., 2006 Jun 9 , 344 (920-5).

524

Tanabe T. et al. Altered pain responses in mice lacking alpha 1E subunit of the voltage-dependent Ca2+ channel.
Proc. Natl. Acad. Sci. U.S.A., 2000 May 23 , 97 (6132-7).

527

Stotz SC. et al. Fast inactivation of voltage-dependent calcium channels. A hinged-lid mechanism?
J. Biol. Chem., 2000 Aug 11 , 275 (24575-82).


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Credits

Editor : Admin.

Contributors : Rajnish Ranjan, Michael Schartner

To cite : [Editor], [Contributors]. Accessed on [Date] Channelpedia , http://channelpedia.epfl.ch/ionchannels/82