Cav2.3
Description: calcium channel, voltage-dependent, R type, alpha 1E subunit Gene: Cacna1e Alias: cacna1e, cav2.3, ca2.3
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].
GeneID: 54234 Cacna1e calcium channel, voltage-dependent, R type, alpha 1E subunit [ Rattus norvegicus ]
Transcript
Species | NCBI accession | Length (nt) | |
---|---|---|---|
Human | NM_001205293.3 | 16420 | |
Mouse | NM_009782.3 | 12697 | |
Rat | NM_019294.3 | 7367 |
Protein Isoforms
Isoforms
Post-Translational Modifications
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]
Cav2.3 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
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].
Biophysics
Model Ca_R (ID=7)
Animal | rat | |
CellType | Cerebellar | |
Age | 21 Days | |
Temperature | 36.0°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 | 2.6/(1+exp((v+7)/-8)) | |
m Beta | 0.18/(1+exp((v+26)/4)) | |
hpower | 1.0 | |
h Alpha | 0.0025/(1+exp((v+32)/8)) | |
h Beta | 0.19/(1+exp((v+42)/-10)) |
Cav2.3 channels are located in dendritic spines. [518]
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].
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]
References
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).
Berrou L
et al.
Molecular determinants of inactivation within the I-II linker of alpha1E (CaV2.3) calcium channels.
Biophys. J.,
2001
Jan
, 80 (215-28).
Pérez-Alvarez A
et al.
Pharmacological and biophysical properties of Ca2+ channels and subtype distributions in human adrenal chromaffin cells.
Pflugers Arch.,
2008
Sep
, 456 (1149-62).
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).
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).
Cohen R
et al.
The C2A domain of synaptotagmin alters the kinetics of voltage-gated Ca2+ channels Ca(v)1.2 (Lc-type) and Ca(v)2.3 (R-type).
J. Biol. Chem.,
2003
Mar
14
, 278 (9258-66).
Berrou L
et al.
A specific tryptophan in the I-II linker is a key determinant of beta-subunit binding and modulation in Ca(V)2.3 calcium channels.
Biophys. J.,
2002
Sep
, 83 (1429-42).
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).
Randall AD
et al.
Contrasting biophysical and pharmacological properties of T-type and R-type calcium channels.
Neuropharmacology,
1997
Jul
, 36 (879-93).
Zhang JF
et al.
Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons.
Neuropharmacology,
1993
Nov
, 32 (1075-88).
Newcomb R
et al.
Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas.
Biochemistry,
1998
Nov
3
, 37 (15353-62).
Wu L
et al.
Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2.
Nature,
2002
Oct
31
, 419 (947-52).
Kuzmiski JB
et al.
Topiramate inhibits the initiation of plateau potentials in CA1 neurons by depressing R-type calcium channels.
Epilepsia,
2005
Apr
, 46 (481-9).
Metz AE
et al.
R-type calcium channels contribute to afterdepolarization and bursting in hippocampal CA1 pyramidal neurons.
J. Neurosci.,
2005
Jun
15
, 25 (5763-73).
Tai C
et al.
Muscarinic enhancement of R-type calcium currents in hippocampal CA1 pyramidal neurons.
J. Neurosci.,
2006
Jun
7
, 26 (6249-58).
Sabatini BL
et al.
Analysis of calcium channels in single spines using optical fluctuation analysis.
Nature,
2000
Nov
30
, 408 (589-93).
Kubota M
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).
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).
Dietrich D
et al.
Functional specialization of presynaptic Cav2.3 Ca2+ channels.
Neuron,
2003
Jul
31
, 39 (483-96).
Yokoyama K
et al.
Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine tolerance.
Eur. J. Neurosci.,
2004
Dec
, 20 (3516-9).
Osanai M
et al.
Altered cerebellar function in mice lacking CaV2.3 Ca2+ channel.
Biochem. Biophys. Res. Commun.,
2006
Jun
9
, 344 (920-5).
Saegusa H
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).
Murakami M
et al.
Antinociceptive effect of different types of calcium channel inhibitors and the distribution of various calcium channel alpha 1 subunits in the dorsal horn of spinal cord in mice.
Brain Res.,
2004
Oct
22
, 1024 (122-9).
Meza U
et al.
Biphasic, opposing modulation of cloned neuronal alpha1E Ca channels by distinct signaling pathways coupled to M2 muscarinic acetylcholine receptors.
J. Neurosci.,
1999
Aug
15
, 19 (6806-17).
Stotz SC
et al.
Fast inactivation of voltage-dependent calcium channels. A hinged-lid mechanism?
J. Biol. Chem.,
2000
Aug
11
, 275 (24575-82).
Contributors: Rajnish Ranjan, Michael Schartner
To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/82/ , accessed on 2024 Mar 19