Cav2.1
Description: calcium channel, voltage-dependent, P/Q type, alpha 1A subunit Gene: Cacna1a Alias: ca2.1, EA2, FHM, MHP, rkr, APCA, HPCA, MHP1, SCA6, Caca1a, Cav2.1, Ccha1a, Cacnl1a4, Cacna1a
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.
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]
Transcript
Species | NCBI accession | Length (nt) | |
---|---|---|---|
Human | NM_000068.4 | 8660 | |
Mouse | NM_007578.3 | 7929 | |
Rat | NM_012918.4 | 8915 |
Protein Isoforms
Isoforms
Post-Translational Modifications
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]
Cav2.1 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
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]
Model Ca_P/Q (ID=5)
Junction potential corrected model
Animal | rat | |
CellType | Cerebellar Purkinje | |
Age | 21 Days | |
Temperature | 21.0°C | |
Reversal | 135.0 mV | |
Ion | Ca + | |
Ligand ion | ||
Reference | [261] T Miyasho et. al; Brain Res. 2001 Feb 9 | |
mpower | 1.0 | |
m Alpha | 8.5/(1+exp((v-8)/(-12.5))) | |
m Beta | 35/(1+exp((v+74)/(14.5))) |
Predominantly expressed in the cerebellar Purkinje cells and granule cells [474].
CaV 2.1 channels are widely distributed in the presynaptic terminals and somatodendritic membranes throughout the brain [474].
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]
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]
References
Miki T
et al.
Two novel alleles of tottering with distinct Ca(v)2.1 calcium channel neuropathologies.
Neuroscience,
2008
Jul
31
, 155 (31-44).
Chen H
et al.
Altered frequency-dependent inactivation and steady-state inactivation of polyglutamine-expanded alpha1A in SCA6.
Am. J. Physiol., Cell Physiol.,
2007
Mar
, 292 (C1078-86).
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).
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).
Hans M
et al.
Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels.
Biophys. J.,
1999
Mar
, 76 (1384-400).
Serra SA
et al.
The hemiplegic migraine-associated Y1245C mutation in CACNA1A results in a gain of channel function due to its effect on the voltage sensor and G-protein-mediated inhibition.
Pflugers Arch.,
2009
Jul
, 458 (489-502).
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).
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).
Dolphin AC
Calcium channel diversity: multiple roles of calcium channel subunits.
Curr. Opin. Neurobiol.,
2009
Jun
, 19 (237-44).
Miyasho T
et al.
Low-threshold potassium channels and a low-threshold calcium channel regulate Ca2+ spike firing in the dendrites of cerebellar Purkinje neurons: a modeling study.
Brain Res.,
2001
Feb
9
, 891 (106-15).
Llinás R
et al.
Distribution and functional significance of the P-type, voltage-dependent Ca2+ channels in the mammalian central nervous system.
Trends Neurosci.,
1992
Sep
, 15 (351-5).
Mintz IM
et al.
P-type calcium channels in rat central and peripheral neurons.
Neuron,
1992
Jul
, 9 (85-95).
Sutton KG
et al.
P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-1A.
Nature,
1999
Oct
21
, 401 (800-4).
Ludwig A
et al.
Regional expression and cellular localization of the alpha1 and beta subunit of high voltage-activated calcium channels in rat brain.
J. Neurosci.,
1997
Feb
15
, 17 (1339-49).
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).
Currie KP
G protein modulation of CaV2 voltage-gated calcium channels.
Channels (Austin),
2010 Nov-Dec
, 4 (497-509).
Mintz IM
et al.
Block of calcium channels in rat neurons by synthetic omega-Aga-IVA.
Neuropharmacology,
1993
Nov
, 32 (1161-9).
Contributors: Rajnish Ranjan, Michael Schartner
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