Channelpedia

Cav2.1

Description: calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Gene: Cacna1a     Synonyms: ca2.1, EA2, FHM, MHP, rkr, APCA, HPCA, MHP1, SCA6, Caca1a, Cav2.1, Ccha1a, Cacnl1a4, Cacna1a

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Introduction

The P/Q-type channels, also known as α1A or Cav2.1, are high voltage activated (HVA) calcium channels widespread throughout cortex. They function in both vesicle release and postsynaptic calcium entry. The α1 subunit is a principal subunit, localized in the cell membrane and forming a conductive pore. β, α2, δ, and γ are auxiliary subunits.

The β subunits are believed to enhance the trafficking of the channels to the plasma membrane by binding via their guanylate kinase (GK)-like domain to the a interaction domain (AID) on the I–II linker of all theHVAa subunits [251].

See also the Channelpedia entry for Cav2.2 which is similar to Cav2.1 in many respects.


Experimental data


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Gene

Genbank 25398, Cacna1a calcium channel, voltage-dependent, P/Q type, alpha 1A subunit [ Rattus norvegicus ], also known as BccA1; rbA-1; Cav2.1; Cacna1a

The alpha 2.1 (alpha 1A) subunits of P-type and Q-type Ca 2+ channels are encoded by a single gene, Cacna1a. [85]

RGD ID Chromosome Position Species
2244 19 25188170-25424495 Rat
10265 8 86939263-87164148 Mouse
735950 19 13317256-13617274 Human

Cacna1a : calcium channel, voltage-dependent, P/Q type, alpha 1A subunit


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Transcript

Acc No Sequence Length Source
NM_012918 n/A n/A NCBI
NM_007578 n/A n/A NCBI
NM_001127221 n/A n/A NCBI
NM_001127222 n/A n/A NCBI
NM_000068 n/A n/A NCBI
NM_001174080 n/A n/A NCBI
NM_023035 n/A n/A NCBI

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Ontology

Accession Name Definition Evidence
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, calmodulin

Omega-agatoxin-IVA

High sensitivity to the funnel web spider venom Omega-agatoxin-IVA. Mintz [555]

Roscovitine

Roscovitine, a potent inhibitor of cyclin-dependent kinases 1, 2, and 5, slows the deactivation of P/Q (Cav2.2) and N-type (CaV2.1) calcium channels. [93]


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Protein


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Structure

When compared with other Ca channels, the Cav2.1 (rbA) channel is notably different in both the carboxyl terminus and in a large (474-amino acid) hydrophilic segment between domains II and HI. [475]


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Distribution

CaV 2.1 channels are widely distributed in the presynaptic terminals and somatodendritic membranes throughout the brain [474].


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Expression

Predominantly expressed in the cerebellar Purkinje cells and granule cells [474].


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Functional

P/Q-type calcium channels (Cav2.1) play an important role in mediating neurotransmitter release in the nervous system, postsynaptic integration, neuroplasticity, neural excitability, and gene transcription [471], [472], [473].

Malfunction of Cav2.1 brings about the disease spinocerebellar ataxia type 6. [83].

Mutations in the gene encoding the pore-forming α1A subunit of P/Q Ca2+ channels (CACNA1A) are linked to familial hemiplegic migraine. [87]


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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.

A detailed compartmental model of a Purkinje neuron, taking into account two types of low-threshold Ca 21 channel (T-type and class-E, or R-type) and two types of low-threshold K 1 channel (A-type and D-type), in addition to another eight voltage-gated channel types, using the program NEURON. [261]

[1] Ca_P/Q (Model ID = 5)

Junction potential corrected model

Animalrat
CellType Cerebellar Purkinje
Age 21 Days
Temperature21.0°C
Reversal 135.0 mV
Ion Ca +
Ligand ion
Reference T Miyasho et. al; Brain Res. 2001 Feb 9
mpower 1.0
mAlpha 8.5/(1+exp((v-8)/(-12.5)))
mBeta 35/(1+exp((v+74)/(14.5)))
40

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References

82

84

Tanaka K et al. Increased Ca2+ channel currents in cerebellar Purkinje cells of the ataxic groggy rat.
Neurosci. Lett., 2007 Oct 16 , 426 (75-80).

85

Tsunemi T et al. Novel Cav2.1 splice variants isolated from Purkinje cells do not generate P-type Ca2+ current.
J. Biol. Chem., 2002 Mar 1 , 277 (7214-21).

251

Dolphin AC Calcium channel diversity: multiple roles of calcium channel subunits.
Curr. Opin. Neurobiol., 2009 Jun , 19 (237-44).

472

Mintz IM et al. P-type calcium channels in rat central and peripheral neurons.
Neuron, 1992 Jul , 9 (85-95).

475

Starr TV et al. Primary structure of a calcium channel that is highly expressed in the rat cerebellum.
Proc. Natl. Acad. Sci. U.S.A., 1991 Jul 1 , 88 (5621-5).

476

Currie KP G protein modulation of CaV2 voltage-gated calcium channels.
Channels (Austin), 2010 Nov-Dec , 4 (497-509).

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/78/ , accessed on [date]