image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Cav1.4

Family: Voltage-gated calcium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Voltage Dependence
Activators
Gating Inhibitors
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 1 1977 Xp11.23 CACNA1F calcium channel, voltage-dependent, L type, alpha 1F subunit 3,20,22
Mouse 24 1 1984 X A1.1 Cacna1f calcium channel, voltage-dependent, alpha 1F subunit 18,23
Rat 24 1 1981 Xq13 Cacna1f calcium channel, voltage-dependent, L type, alpha 1F subunit 16
Previous and Unofficial Names
alpha1F
Cav1.4
L-type
α1F
CSNB2
AIED
JM8
JMC8
CSNBX2
CORDX3
CSNB2A
COD4
OA2
Aland island eye disease (Forsius-Eriksson ocular albinism, ocular albinism type 2)
calcium channel, voltage-dependent, L type, alpha 1F subunit
calcium channel, voltage-dependent, alpha 1F subunit
voltage-dependent L-type calcium channel subunit alpha-1F
Sfc17
nerg1
nob2
Database Links
ChEMBL Target 18021 (Hs)
DrugBank Target 4113 (Hs)
Ensembl ENSG00000102001 (Hs), ENSMUSG00000031142 (Mm), ENSRNOG00000010348 (Rn)
Entrez Gene 778 (Hs), 54652 (Mm), 114493 (Rn)
GeneCards CACNA1F (Hs)
GenitoUrinary Development Molecular Anatomy Project Cacna1f (Mm)
HomoloGene 74542 (Hs)
Human Protein Reference Database 02119 (Hs)
InterPro O60840 (Hs), Q9J1S7 (Mm)
KEGG Gene hsa:778 (Hs), mmu:54652 (Mm), rno:114493 (Rn)
OMIM 2344 (Hs), 300110 (Hs)
Orphanet Gene ORPHA119148 (Hs)
PharmGKB Gene PA26010 (Hs)
PhosphoSitePlus O60840 (Hs), Q9JIS7 (Mm), A1XIQ4 (Rn)
Protein Ontology (PRO) PRO:000002115 (Hs)
RefSeq Nucleotide NM_005183 (Hs), NM_019582 (Mm), NM_053701 (Rn)
RefSeq Protein NP_005174 (Hs), NP_062528 (Mm), NP_446153 (Rn)
TreeFam ENSG00000102001 (Hs), ENSMUSG00000031142 (Mm), ENSRNOG00000010348 (Rn)
UniGene Hs. 632799 (Hs)
UniProt O60840 (Hs), Q9J1S7 (Mm)
Wikipedia Cav1.4
Voltage-gated calcium channels
Search for 3D structures on the PDB
Search by keyword: Voltage-gated calcium channels Cav1.4 Search by accession number: Q9J1S7, O60840
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
α2δ 12,19
β (likely β2) 1
Other Associated Proteins
Name References
Not determined
Ion Selectivity and Conductance
Species:  Human
Rank order:  Cs+ [21.0 pS] > Ba2+ [4.0 pS]
References:  7
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -11.6 – 0.6 0.43 – 6.6 13,15,20 tsA-201 cells. Human
Inactivation  -9.3 9.8 15
Comments  Data are for ICa2+, except for τ which was determined for IBa2+. V0.5 for activation is more positive with Ca2+ as a charge carrier than with Ba2+. Unlike for other Ca2+ channels, Ca2+-dependent inactivation (CDI) is absent due to inhibition of CDI by a C-terminal modulatroy domain [20,23]. ICa2+ inactivates by about 80% during 10-s depolarisations to Vmax [13,20,23]. Activation is biexponential with β2 subunits (τ for fast and slow phase are given).
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -15.4 – -1.1 (median: -12.0) 0.65 – 3.6 2,9 HEK 293 cells. Mouse
Inactivation  - - 2
Comments  Data are for ICa2+, except for τ which was determined for IBa2+. V0.5 for activation is more positive with Ca2+ as a charge carrier than with Ba2+.
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
BAYK 8644 Hs - - 5x10-6 - 1x10-5 -100.0 – -80.0 11,13,15
BAYK 8644 Mm - - 1x10-6 -80.0 2
View species-specific activator tables
Activator Comments
BAYK 8644 shifts the I-V relationship 5-10mV in the hyperpolarised direction.
Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
verapamil Mm - - 1x10-4 -80.0 2
isradipine Hs - - 1x10-6 -90.0 – -50.0 13
isradipine Mm 6.7 pIC50 - -80.0 2
nifedipine Hs 6.0 pIC50 - -100.0 15
L-(cis)-diltiazem Mm 4.1 pIC50 - -80.0 2
diltiazem Mm 4.0 pIC50 - -80.0 2
View species-specific gating inhibitor tables
Gating Inhibitor Comments
The effect of (+/-)-isradipine is voltage-depepndant with 100nM producing 20-42% current block at a holding potential of -80 - -90mV and 80-90% block at -50mV [2,13]. Nifedipine also shows a mild increase in block at more positive holding voltages [15].

(+)-[3H]-isradipine does not show any high affinity binding with Cav1.4 [21].
Tissue Distribution
Retina (outer plexiform layer, inner plexiform and nuclear layer)
Species:  Human
Technique:  Immunohistochemistry
References:  15
Lymphoid tissues, plasma, mast cells
Species:  Human
Technique:  Immunohistochemistry
References:  15
T-lymphocytes
Species:  Human
Technique:  RT-PCR, immunoprecipitation
References:  14
Retina
Species:  Human
Technique:  RT-PCR
References:  3,15
Retina
Species:  Human
Technique:  Northern Blot
References:  22
Retina (inner and outer nuclear layer, ganglion cell layer).
Species:  Mouse
Technique:  In situ hybridisation
References:  22
Dorsal root ganglia
Species:  Mouse
Technique:  RT-PCR
References:  17
Functional Assays
Electrophysiology (whole-cell voltage clamp).
Species:  Human
Tissue:  HEK-293 cells expressing Cav1.4.
Response measured:  L-type currents.
References:  13,15,20
Electrophysiology (whole-cell voltage clamp)
Species:  Mouse
Tissue:  HEK-293 cells expressing Cav1.4.
Response measured:  L-type currents
References:  2,9,23
Electrophysiology (single channel recording).
Species:  Human
Tissue:  HEK-293 cells expressing Cav1.4
Response measured:  L-type currents
References:  7
Electrophysiology (two electrode voltage clamp).
Species:  Human
Tissue:  Xenopus laevis oocytes expressing Cav1.4
Response measured:  L-type currents.
References:  11
Physiological Functions
Retinal signaling; neurotransmitter release from photoreceptors
Species:  Mouse
Tissue:  Retina
References:  6
Physiological Consequences of Altering Gene Expression
An abnormal light- and dark-adapted electroretinogram and a disorganised outer plexiform layer can be seen in the nob2 mouse (null mutation in Cacna1f ).
Species:  Mouse
Tissue:  Retina
Technique:  Natural mutation
References:  6,8
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cacna1fnob2 Cacna1fnob2/Cacna1fnob2
AXB6/PgnJ		 MGI:1859639  MP:0004022 abnormal cone electrophysiology PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Y
AXB6/PgnJ		 MGI:1859639  MP:0004022 abnormal cone electrophysiology PMID: 16597347 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Y
B6.129-Cacna1f		 MGI:1859639  MP:0005551 abnormal eye electrophysiology PMID: 16155113 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Cacna1ftm1Ntbh
B6.129-Cacna1f		 MGI:1859639  MP:0005551 abnormal eye electrophysiology PMID: 16155113 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Y
B6.129-Cacna1f		 MGI:1859639  MP:0006068 abnormal horizontal cell morphology PMID: 16155113 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Cacna1ftm1Ntbh
B6.129-Cacna1f		 MGI:1859639  MP:0006068 abnormal horizontal cell morphology PMID: 16155113 
Cacna1fnob2 Cacna1fnob2/Cacna1fnob2
AXB6/PgnJ		 MGI:1859639  MP:0006068 abnormal horizontal cell morphology PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Y
AXB6/PgnJ		 MGI:1859639  MP:0006068 abnormal horizontal cell morphology PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Cacna1fnob2
AXB6/PgnJ		 MGI:1859639  MP:0008056 abnormal retinal ganglion cell morphology PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Y
AXB6/PgnJ		 MGI:1859639  MP:0008056 abnormal retinal ganglion cell morphology PMID: 16597347 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Y
B6.129-Cacna1f		 MGI:1859639  MP:0006069 abnormal retinal neuronal layer morphology PMID: 16155113 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Cacna1ftm1Ntbh
B6.129-Cacna1f		 MGI:1859639  MP:0006069 abnormal retinal neuronal layer morphology PMID: 16155113 
Cacna1fnob2 Cacna1fnob2/Cacna1fnob2
AXB6/PgnJ		 MGI:1859639  MP:0003731 abnormal retinal outer nuclear layer morphology PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Y
AXB6/PgnJ		 MGI:1859639  MP:0003731 abnormal retinal outer nuclear layer morphology PMID: 16597347 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Y
B6.129-Cacna1f		 MGI:1859639  MP:0006074 abnormal retinal rod bipolar cell morphology PMID: 16155113 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Cacna1ftm1Ntbh
B6.129-Cacna1f		 MGI:1859639  MP:0006074 abnormal retinal rod bipolar cell morphology PMID: 16155113 
Cacna1fnob2 Cacna1fnob2/Cacna1fnob2
AXB6/PgnJ		 MGI:1859639  MP:0006074 abnormal retinal rod bipolar cell morphology PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Y
AXB6/PgnJ		 MGI:1859639  MP:0006074 abnormal retinal rod bipolar cell morphology PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Cacna1fnob2
AXB6/PgnJ		 MGI:1859639  MP:0004021 abnormal rod electrophysiology PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Y
AXB6/PgnJ		 MGI:1859639  MP:0004021 abnormal rod electrophysiology PMID: 16597347 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Y
B6.129-Cacna1f		 MGI:1859639  MP:0000968 abnormal sensory neuron innervation pattern PMID: 16155113 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Cacna1ftm1Ntbh
B6.129-Cacna1f		 MGI:1859639  MP:0000968 abnormal sensory neuron innervation pattern PMID: 16155113 
Cacna1fnob2 Cacna1fnob2/Cacna1fnob2
AXB6/PgnJ		 MGI:1859639  MP:0008520 disorganized retinal outer plexiform layer PMID: 16597347 
Cacna1fnob2 Cacna1fnob2/Y
AXB6/PgnJ		 MGI:1859639  MP:0008520 disorganized retinal outer plexiform layer PMID: 16597347 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Y
B6.129-Cacna1f		 MGI:1859639  MP:0008519 thin retinal outer plexiform layer PMID: 16155113 
Cacna1ftm1Ntbh Cacna1ftm1Ntbh/Cacna1ftm1Ntbh
B6.129-Cacna1f		 MGI:1859639  MP:0008519 thin retinal outer plexiform layer PMID: 16155113 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Congenital staionary night blindness type 2 (CSNB2)
OMIM:  300071
Orphanet:  215
Role:  Decreased signaling from photoreceptors to secondary neurons
Drugs:  Not established
References:  3,6,22
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human I1003 4
Deletion Human F318 4
Deletion Human 3720-3731 (mRNA) 22
Frameshift Human I1159insC 3
Frameshift Human L1056insC 5
Frameshift Human L991insC 3
Frameshift Human D341delC 3
Frameshift Human 213del5bp 24
Frameshift Human 5727delG 4
Frameshift Human 3735delC (mRNA) 4
Frameshift Human 3228insC (mRNA) 4
Frameshift Human 3195insC (mRNA) 22
Frameshift Human 3187delG 4
Frameshift Human 1280delC (mRNA) 4
Missense Human L1497P 24
Missense Human P1489R 24
Missense Human C1488R 24
Missense Human L1364H 11,22
Missense Human L1068P 10,24
Missense Human R1049W 22
Missense Human G1007R 24
Missense Human A928D 4,15
Missense Human L849P 24
Missense Human F742C 24
Missense Human G674D 4,15
Missense Human R508Q 11,22
Missense Human G369D 10,15,22
Missense Human G261R 24
Missense Human S229P 10,24
Truncation Human R1816X 24
Truncation Human K1591X 20,22
Truncation Human W1451X 4
Truncation Human W1386X 3
Truncation Human R1299X 4
Truncation Human R1288X 24
Truncation Human R1234X 3
Truncation Human R958X 22
Truncation Human R895X 4
Truncation Human R625X 4
Truncation Human R614X 24
Truncation Human Q428X 24
Truncation Human R380X 3
Truncation Human R82X 4,24
Truncation Human R50X 4
Disease:  Cone-rod dystrophy, X-linked, 3
OMIM:  300476
Orphanet:  1872
References: 
Mutations not determined
Disease:  Aland Island eye disease; AIED
OMIM:  300600
Orphanet:  178333
References: 
Mutations not determined
Clinically-Relevant Mutations and Pathophysiology Comments
Mutations in intronic sequences of the Cav gene have also been associated with CSNB2 [4]. The electrophysiological consequences of several of these mutations have been investigated in heterologous expression systems [10-11,15,20,23]

REFERENCES

Show »

1. Ball, SL; Powers, PA; Shin, HS; Morgans, CW; Peachey, NS; Gregg, RG. (2002) Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer. Invest. Ophthalmol. Vis. Sci., 43 (5): 1595-603. [PMID:11980879]

2. Baumann, L; Gerstner, A; Zong, X; Biel, M; Wahl-Schott, C. (2004) Functional characterization of the L-type Ca2+ channel Cav1.4alpha1 from mouse retina. Invest. Ophthalmol. Vis. Sci., 45 (2): 708-13. [PMID:14744918]

3. Bech-Hansen, NT; Naylor, MJ; Maybaum, TA; Pearce, WG; Koop, B; Fishman, GA; Mets, M; Musarella, MA; Boycott, KM. (1998) Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. Nat. Genet., 19 (3): 264-7. [PMID:9662400]

4. Boycott, KM; Maybaum, TA; Naylor, MJ; Weleber, RG; Robitaille, J; Miyake, Y; Bergen, AA; Pierpont, ME; Pearce, WG; Bech-Hansen, NT. (2001) A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants. Hum. Genet., 108 (2): 91-7. [PMID:11281458]

5. Boycott, KM; Pearce, WG; Bech-Hansen, NT. (2000) Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F. Can. J. Ophthalmol., 35 (4): 204-13. [PMID:10900517]

6. Chang, B; Heckenlively, JR; Bayley, PR; Brecha, NC; Davisson, MT; Hawes, NL; Hirano, AA; Hurd, RE; Ikeda, A; Johnson, BA; McCall, MA; Morgans, CW; Nusinowitz, S; Peachey, NS; Rice, DS; Vessey, KA; Gregg, RG. (2006) The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses. Vis. Neurosci., 23 (1): 11-24. [PMID:16597347]

7. Doering, CJ; Hamid, J; Simms, B; McRory, JE; Zamponi, GW. (2005) Cav1.4 encodes a calcium channel with low open probability and unitary conductance. Biophys. J., 89 (5): 3042-8. [PMID:16085774]

8. Doering, CJ; Rehak, R; Bonfield, S; Peloquin, JB; Stell, WK; Mema, SC; Sauvé, Y; McRory, JE. (2008) Modified Ca(v)1.4 expression in the Cacna1f(nob2) mouse due to alternative splicing of an ETn inserted in exon 2. PLoS ONE, 3 (7): e2538. [PMID:18596967]

9. Haeseleer, F; Imanishi, Y; Maeda, T; Possin, DE; Maeda, A; Lee, A; Rieke, F; Palczewski, K. (2004) Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function. Nat. Neurosci., 7 (10): 1079-87. [PMID:15452577]

10. Hoda, JC; Zaghetto, F; Koschak, A; Striessnig, J. (2005) Congenital stationary night blindness type 2 mutations S229P, G369D, L1068P, and W1440X alter channel gating or functional expression of Ca(v)1.4 L-type Ca2+ channels. J. Neurosci., 25 (1): 252-9. [PMID:15634789]

11. Hoda, JC; Zaghetto, F; Singh, A; Koschak, A; Striessnig, J. (2006) Effects of congenital stationary night blindness type 2 mutations R508Q and L1364H on Cav1.4 L-type Ca2+ channel function and expression. J. Neurochem., 96 (6): 1648-58. [PMID:16476079]

12. Klugbauer, N; Marais, E; Hofmann, F. (2003) Calcium channel alpha2delta subunits: differential expression, function, and drug binding. J. Bioenerg. Biomembr., 35 (6): 639-47. [PMID:15000524]

13. Koschak, A; Reimer, D; Walter, D; Hoda, JC; Heinzle, T; Grabner, M; Striessnig, J. (2003) Cav1.4alpha1 subunits can form slowly inactivating dihydropyridine-sensitive L-type Ca2+ channels lacking Ca2+-dependent inactivation. J. Neurosci., 23 (14): 6041-9. [PMID:12853422]

14. Kotturi, MF; Jefferies, WA. (2005) Molecular characterization of L-type calcium channel splice variants expressed in human T lymphocytes. Mol. Immunol., 42 (12): 1461-74. [PMID:15899519]

15. McRory, JE; Hamid, J; Doering, CJ; Garcia, E; Parker, R; Hamming, K; Chen, L; Hildebrand, M; Beedle, AM; Feldcamp, L; Zamponi, GW; Snutch, TP. (2004) The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution. J. Neurosci., 24 (7): 1707-18. [PMID:14973233]

16. Morgans, CW; Gaughwin, P; Maleszka, R. (2001) Expression of the alpha1F calcium channel subunit by photoreceptors in the rat retina. Mol. Vis., 7: 202-9. [PMID:11526344]

17. Murakami, M; Nakagawasai, O; Fujii, S; Kameyama, K; Murakami, S; Hozumi, S; Esashi, A; Taniguchi, R; Yanagisawa, T; Tan-no, K; Tadano, T; Kitamura, K; Kisara, K. (2001) Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur. J. Pharmacol., 419 (2-3): 175-81. [PMID:11426839]

18. Naylor, MJ; Rancourt, DE; Bech-Hansen, NT. (2000) Isolation and characterization of a calcium channel gene, Cacna1f, the murine orthologue of the gene for incomplete X-linked congenital stationary night blindness. Genomics, 66 (3): 324-7. [PMID:10873387]

19. Qin, N; Yagel, S; Momplaisir, ML; Codd, EE; D'Andrea, MR. (2002) Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit. Mol. Pharmacol., 62 (3): 485-96. [PMID:12181424]

20. Singh, A; Hamedinger, D; Hoda, JC; Gebhart, M; Koschak, A; Romanin, C; Striessnig, J. (2006) C-terminal modulator controls Ca2+-dependent gating of Ca(v)1.4 L-type Ca2+ channels. Nat. Neurosci., 9 (9): 1108-16. [PMID:16921373]

21. Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J. (2008) Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol., Epub (issue number): pages. [PMID:19029287]

22. Strom, TM; Nyakatura, G; Apfelstedt-Sylla, E; Hellebrand, H; Lorenz, B; Weber, BH; Wutz, K; Gutwillinger, N; Rüther, K; Drescher, B; Sauer, C; Zrenner, E; Meitinger, T; Rosenthal, A; Meindl, A. (1998) An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. Nat. Genet., 19 (3): 260-3. [PMID:9662399]

23. Wahl-Schott, C; Baumann, L; Cuny, H; Eckert, C; Griessmeier, K; Biel, M. (2006) Switching off calcium-dependent inactivation in L-type calcium channels by an autoinhibitory domain. Proc. Natl. Acad. Sci. U.S.A., 103 (42): 15657-62. [PMID:17028172]

24. Wutz, K; Sauer, C; Zrenner, E; Lorenz, B; Alitalo, T; Broghammer, M; Hergersberg, M; de la Chapelle, A; Weber, BH; Wissinger, B; Meindl, A; Pusch, CM. (2002) Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina. Eur. J. Hum. Genet., 10 (8): 449-56. [PMID:12111638]

To cite this database page, please use the following:

William A. Catterall, Edward Perez-Reyes, Terrance P. Snutch, Joerg Striessnig.
Voltage-gated calcium channels: Cav1.4. Last modified on 05/02/2013. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=531.


Contact us | Print | Back to top | Help