Cav1.2
Description: calcium channel, voltage-dependent, L type, alpha 1C subunit Gene: Cacna1c Alias: cacna1c, cav1.2, ca1.2
Voltage-gated Ca2+ channels fall in three different groups: Cav1(L-type), Cav2 (N–, P/Q–, R-types), and Cav3 (T-type) [226]. Cav1.2 is an L type, high voltage activated (HVA) calcium channel found in neurons. It is also known as a1C.
GeneID: 29716 Cacna1d calcium channel, voltage-dependent, L type, alpha 1D subunit [ Rattus norvegicus ]
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_199460.4 | 13993 | |
| Mouse | NM_009781.4 | 13340 | |
| Rat | NM_012517.2 | 8257 |
Protein Isoforms
Isoforms
Post-Translational Modifications
Their pore-forming alpha 1-subunit is composed of four homologous domains formed by six transmembrane segments (S1–S6) [477]. The signal of the voltage-sensing machinery, consisting of multiple charged amino acids (located in segments S4 and adjacent structures of each domain), is transmitted to the pore region [499]. Conformational changes in pore lining S6 and adjacent segments finally lead to pore openings (activation) and closures (inactivation).
Compared with potassium channels, the pore of CaV is asymmetric, and none of the four S6 segments has a putative helixbending PXP motif. Furthermore, the conserved glycine (corresponding to position 83 in MthK, see [500]) is only present in segments IS6 and IIS6 (for review see [501]). Substituting proline for this glycine in IIS6 of CaV1.2 does not significantly affect gating [502].
IS6 and IIS6 residues contribute in a energetically coupled way to activation gating.[225]
Cav1.2 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
Whereas all voltage-gated Ca2+ channel alpha-1 subunits activate and in- activate in response to membrane depolarization, the high voltage activated CaV1 and CaV2 alpha-1 subunits operate at markedly more positive membrane potentials than low voltage activated CaV3 channel alpha-1 subunits. [227]
In cardiac myocytes, the α1C subunit of L-type Ca2+ channels (Cav1.2) is the dominant Ca channel. [226]
Ca2+ current through CaV1.2 channels initiates muscle con- traction, release of hormones and neurotransmitters, and affects physiological processes such as vision, hearing, and gene expression [498].
Second Messanger-activated Protein Kinases
Ca2+ channels are regulated primarily by second messenger-activated protein kinases. [503]
kir/Gem
The small G-protein kir/Gem inhibits L- type Ca2+ channel activities by interacting directly with the Ca2+ channel β subunit [504].
COP9 signalosome subunit 5
COP9 signalosome subunit 5 (CSN5)/Jun activation domain-binding protein 1 (Jab1) interacts with the II–III linker of the α1C subunit. Inhibi- tion of CSN5 expression by siRNA enhanced the L-type Ca2+ currents. CSN5 regulates the cardiac L-type Ca2+ channel through protein–protein interactions. [226]
References
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et al.
Coupled and independent contributions of residues in IS6 and IIS6 to activation gating of CaV1.2.
J. Biol. Chem.,
2009
May
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Kameda K
et al.
CSN5/Jab1 inhibits cardiac L-type Ca2+ channel activity through protein-protein interactions.
J. Mol. Cell. Cardiol.,
2006
Apr
, 40 (562-9).
Dafi O
et al.
Negatively charged residues in the N-terminal of the AID helix confer slow voltage dependent inactivation gating to CaV1.2.
Biophys. J.,
2004
Nov
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Catterall WA
Structure and regulation of voltage-gated Ca2+ channels.
Annu. Rev. Cell Dev. Biol.,
2000
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Catterall WA
et al.
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Jiang Y
et al.
The principle of gating charge movement in a voltage-dependent K+ channel.
Nature,
2003
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Jiang Y
et al.
The open pore conformation of potassium channels.
Nature,
2002
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30
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Hering S
et al.
Pore stability and gating in voltage-activated calcium channels.
Channels (Austin),
2008 Mar-Apr
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Hohaus A
et al.
Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder.
J. Biol. Chem.,
2005
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Reuter H
Calcium channel modulation by neurotransmitters, enzymes and drugs.
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Béguin P
et al.
Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem.
Nature,
2001
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Contributors: Rajnish Ranjan, Michael Schartner
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