Cav1.4
Description: calcium channel, voltage-dependent, L type, alpha 1F subunit Gene: Cacna1f Alias: cacna1f, cav1.4, ca1.4
Voltage-gated calcium channels (VGCCs), heteromultimeric protein complexes consisting of an alpha1 sub- unit, as well as ancillary beta, alpha2-delta, and possibly gamma subunits (Hofmann et al., 1994 [1220]), are a primary route through which calcium can enter cells.
CACNA1 (also known as JM8; OA2; AIED; COD3; COD4; JMC8; CORDX; CSNB2; CORDX3; CSNB2A; CSNBX2; Cav1.4 encodes Cav1.4, a member of the alpha-1 subunit family, L type, high voltage activated (HVA) calcium channel, found in the retina. It is also known as a1F. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants of the gene described here have been observed but have not been thoroughly characterized. Mutations in this gene have been shown to cause incomplete X-linked congential stationary night blindness type 2 (CSNB2).
http://www.ncbi.nlm.nih.gov/gene/778
VGCCs are encoded by 10 genes, four of which encode the L-type calcium channel family and include Cav1.1, Cav1.2, Cav1.3 and Cav1.4 (Ertel et al., 2000 [1224]).
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_005183.4 | 6039 | |
| Mouse | NM_019582.2 | 6075 | |
| Rat | NM_053701.2 | 5976 |
Protein Isoforms
Isoforms
Post-Translational Modifications
Voltage-gated calcium channels (VGCCs), heteromultimeric protein complexes consisting of an alpha1 sub- unit, as well as ancillary beta, alpha2-delta, and possibly gamma subunits (Hofmann et al., 1994 [1220]), are a primary route through which calcium can enter cells. The alpha1 subunit forms the ion conducting pore and contains the ion selectivity filter and voltage sensors which gate the channel in response to changes in membrane potential (Hofmann et al., 1994 [1220]). Auxiliary beta and alpha2-delta subunits modulate channel kinetics and targeting of the alpha1 subunit to the membrane (Neely et al., 1993 [1221]; Tareilus et al., 1997 [1222]; Yasuda et al., 2004 [1223]).
Cav1.4 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
Cav1.4 channels have fast activation kinetics, ultraslow inactivation kinetics that may be the result of late openings, and the presence of a large window current which ranges from -20 mV to +20 mV (Koschak et al., 2003 [1226]; McRory et al., 2004 [233]; Doering et al., 2007 [1219]) at room temperature in 15 or 20 mM Ba2+.
The Cav1.4 VGCC is expressed in the retina and localizes at ribbon synapses in cone and rod photoreceptors (Morgans et al., 2005 [1225]), as well as in the inner nuclear and ganglion cell layer (McRory et al., 2004 [233]). The channel is also detectable in plasma and mast cells, although its role in the immune system is not fully understood. (Peloquin [232])
See expression.
Cav1.4 channels may be ideally suited to support tonic release of glutamate at the ribbon synapse under constantly depolarized conditions. (Peloquin [232])
Temperature dependence of Cav1.4: With 20 mM Ba2+ as charge carrier, increasing the temperature from 23 °C to 37 °C increases whole-cell conductance, shifts the voltage-dependence of activation to more hyperpolarized voltages, and accelerates the degree of recovery from inactivation over a given time, but does not significantly alter the half-inactivation potential (Vh). (Peloquin [232])
References
Hemara-Wahanui A
et al.
A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation.
Proc. Natl. Acad. Sci. U.S.A.,
2005
May
24
, 102 (7553-8).
Peloquin JB
et al.
Temperature dependence of Cav1.4 calcium channel gating.
Neuroscience,
2008
Feb
19
, 151 (1066-83).
McRory JE
et al.
The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution.
J. Neurosci.,
2004
Feb
18
, 24 (1707-18).
Doering CJ
et al.
Cav1.4 encodes a calcium channel with low open probability and unitary conductance.
Biophys. J.,
2005
Nov
, 89 (3042-8).
Hofmann F
et al.
Molecular basis for Ca2+ channel diversity.
Annu. Rev. Neurosci.,
1994
, 17 (399-418).
Neely A
et al.
Potentiation by the beta subunit of the ratio of the ionic current to the charge movement in the cardiac calcium channel.
Science,
1993
Oct
22
, 262 (575-8).
Tareilus E
et al.
A Xenopus oocyte beta subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit.
Proc. Natl. Acad. Sci. U.S.A.,
1997
Mar
4
, 94 (1703-8).
Yasuda T
et al.
Auxiliary subunit regulation of high-voltage activated calcium channels expressed in mammalian cells.
Eur. J. Neurosci.,
2004
Jul
, 20 (1-13).
Morgans CW
Localization of the alpha(1F) calcium channel subunit in the rat retina.
Invest. Ophthalmol. Vis. Sci.,
2001
Sep
, 42 (2414-8).
Koschak A
et al.
Cav1.4alpha1 subunits can form slowly inactivating dihydropyridine-sensitive L-type Ca2+ channels lacking Ca2+-dependent inactivation.
J. Neurosci.,
2003
Jul
9
, 23 (6041-9).
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