Cav1.3

Description: calcium channel, voltage-dependent, L type, alpha 1D subunit
Gene: Cacna1d
Alias: cacna1d, cav1.3, ca1.3

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Introduction

Cav1.3 is an L type, high voltage activated (HVA) calcium channel found in the certain neuronal dendrites. It is also known as a1E. Its role in hair cells has been studied [228], [229].

Four L-type voltage gated Ca channels (LTCC) isoforms evolved (termed Cav1.1, Cav1.2, Cav1.3, and Cav1.4). All of them are characterized by high sensitivity to dihydropyridine (DHP) Ca2+ channel modulators, although differences in their voltage-dependence of DHP block exist [511]. This unique DHP sensitivity distinguishes them from other voltage-gated Ca2+ channel types (non-LTCCs). LTCC isoforms differ considerably with respect to their gating properties and tissue expression [511]. The gating differences are intrinsic properties of their pore-forming alpha-1 subunits which assemble with accessory alpha-2-delta and beta-subunits (and in some tissues also a gamma-subunit) to form a functional channel complex [511].

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Gene

Species	NCBI gene ID	Chromosome	Position
Human	776	3	319122
Mouse	12289	14	451215
Rat	29716	16	294006

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_000720.4	9429
Mouse	NM_028981.3	8701
Rat	NM_001389225.1	9071

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	Q01668	2161
Mouse	Q99246	2179
Rat	P27732	2203

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_001128840.3

9369

NP_001122312.1

2161

transcript variant 2

isoform b

NM_001128839.3

9297

NP_001122311.1

2137

transcript variant 3

isoform c

NM_000720.4

9429

NP_000711.1

2181

transcript variant 1

isoform a

Predicted

XM_005265448.4

9324

XP_005265505.1

2146

transcript variant X14

isoform X14

XM_047448874.1

12237

XP_047304830.1

1632

transcript variant X18

isoform X18

XM_011534094.3

9083

XP_011532396.1

2246

transcript variant X2

isoform X2

XM_017007144.2

8999

XP_016862633.1

2218

transcript variant X8

isoform X8

XM_017007141.2

9023

XP_016862630.1

2226

transcript variant X6

isoform X6

XM_017007137.2

9083

XP_016862626.1

2246

transcript variant X1

isoform X1

XM_017007139.2

9056

XP_016862628.1

2237

transcript variant X4

isoform X4

XM_047448871.1

9011

XP_047304827.1

2222

transcript variant X7

isoform X7

XM_017007142.2

8999

XP_016862631.1

2218

transcript variant X10

isoform X10

XM_017007145.2

8954

XP_016862634.1

2203

transcript variant X11

isoform X11

XM_047448872.1

8927

XP_047304828.1

2194

transcript variant X12

isoform X12

XM_017007143.2

8999

XP_016862632.1

2218

transcript variant X9

isoform X9

XM_017007138.2

9080

XP_016862627.1

2245

transcript variant X3

isoform X3

XM_017007140.2

9023

XP_016862629.1

2226

transcript variant X5

isoform X5

XM_011534100.3

8978

XP_011532402.1

2211

transcript variant X19

isoform X19

XM_011534096.3

8894

XP_011532398.1

2183

transcript variant X13

isoform X13

XM_047448873.1

5604

XP_047304829.1

1656

transcript variant X17

isoform X17

XM_011534097.3

9550

XP_011532399.1

2067

transcript variant X15

isoform X15

XM_011534099.3

8535

XP_011532401.1

1942

transcript variant X16

isoform X16

XM_054347781.1

9320

XP_054203756.1

2146

transcript variant X14

isoform X14

XM_054347785.1

11587

XP_054203760.1

1632

transcript variant X18

isoform X18

XM_054347769.1

9079

XP_054203744.1

2246

transcript variant X2

isoform X2

XM_054347775.1

8995

XP_054203750.1

2218

transcript variant X8

isoform X8

XM_054347773.1

9019

XP_054203748.1

2226

transcript variant X6

isoform X6

XM_054347768.1

9079

XP_054203743.1

2246

transcript variant X1

isoform X1

XM_054347771.1

9052

XP_054203746.1

2237

transcript variant X4

isoform X4

XM_054347774.1

9007

XP_054203749.1

2222

transcript variant X7

isoform X7

XM_054347777.1

8995

XP_054203752.1

2218

transcript variant X10

isoform X10

XM_054347778.1

8950

XP_054203753.1

2203

transcript variant X11

isoform X11

XM_054347779.1

8923

XP_054203754.1

2194

transcript variant X12

isoform X12

XM_054347776.1

8995

XP_054203751.1

2218

transcript variant X9

isoform X9

XM_054347770.1

9076

XP_054203745.1

2245

transcript variant X3

isoform X3

XM_054347772.1

9019

XP_054203747.1

2226

transcript variant X5

isoform X5

XM_054347786.1

8974

XP_054203761.1

2211

transcript variant X19

isoform X19

XM_054347780.1

8890

XP_054203755.1

2183

transcript variant X13

isoform X13

XM_054347784.1

9271

XP_054203759.1

1656

transcript variant X17

isoform X17

XM_054347782.1

9543

XP_054203757.1

2067

transcript variant X15

isoform X15

XM_054347783.1

8531

XP_054203758.1

1942

transcript variant X16

isoform X16

Known

NM_028981.3

8701

NP_083257.2

2166

transcript variant 1

isoform 1

NM_001083616.2

9075

NP_001077085.1

2144

transcript variant 2

isoform 2

NM_001302637.1

9180

NP_001289566.1

2179

transcript variant 3

isoform 3

Predicted

XR_001781092.3

9009

transcript variant X19

XR_004938371.1

5760

transcript variant X22

XM_017315824.3

9101

XP_017171313.1

2144

transcript variant X25

isoform X23

XM_017315823.3

9185

XP_017171312.1

2172

transcript variant X24

isoform X22

XM_017315811.3

9230

XP_017171300.1

2187

transcript variant X6

isoform X6

XM_036158415.1

9160

XP_036014308.1

2206

transcript variant X3

isoform X3

XM_017315819.3

8950

XP_017171308.1

2136

transcript variant X16

isoform X16

XM_017315817.3

8995

XP_017171306.1

2151

transcript variant X13

isoform X13

XM_017315815.3

9034

XP_017171304.1

2164

transcript variant X10

isoform X10

XM_017315813.3

9079

XP_017171302.1

2179

transcript variant X8

isoform X8

XM_017315816.3

9034

XP_017171305.1

2164

transcript variant X11

isoform X11

XM_017315810.3

9118

XP_017171299.1

2192

transcript variant X5

isoform X5

XM_036158416.1

8986

XP_036014309.1

2148

transcript variant X14

isoform X14

XM_017315809.3

9136

XP_017171298.1

2198

transcript variant X4

isoform X4

XM_006518475.3

9163

XP_006518538.1

2207

transcript variant X1

isoform X1

XM_017315825.3

8883

XP_017171314.1

2144

transcript variant X26

isoform X24

XM_006518480.3

8856

XP_006518543.1

2135

transcript variant X17

isoform X17

XM_006518479.3

8928

XP_006518542.1

2159

transcript variant X12

isoform X12

XM_017315812.3

9012

XP_017171301.1

2187

transcript variant X7

isoform X7

XM_017315814.3

8988

XP_017171303.1

2179

transcript variant X9

isoform X9

XM_017315808.3

9072

XP_017171297.1

2207

transcript variant X2

isoform X2

XM_017315818.3

8833

XP_017171307.1

2139

transcript variant X15

isoform X15

XM_036158417.1

7559

XP_036014310.1

1803

transcript variant X18

isoform X18

XM_017315820.3

12572

XP_017171309.1

1709

transcript variant X20

isoform X19

XM_017315821.3

5589

XP_017171310.1

1695

transcript variant X21

isoform X20

XM_036158419.1

4605

XP_036014312.1

1345

transcript variant X23

isoform X21

Known

NM_001389225.1

9071

NP_001376154.1

2164

Predicted

XR_005494599.1

12565

transcript variant X19

XR_005494598.1

12495

transcript variant X18

XR_005494597.1

12624

transcript variant X17

XM_017600059.2

9165

XP_017455548.1

2187

transcript variant X6

isoform X6

XM_039094434.1

9222

XP_038950362.1

2206

transcript variant X3

isoform X3

XM_017600065.2

9012

XP_017455554.1

2136

transcript variant X14

isoform X14

XM_017600064.2

9096

XP_017455553.1

2164

transcript variant X11

isoform X11

XM_017600061.2

9141

XP_017455550.1

2179

transcript variant X9

isoform X9

XM_017600058.2

9180

XP_017455547.1

2192

transcript variant X5

isoform X5

XM_017600057.2

9198

XP_017455546.1

2198

transcript variant X4

isoform X4

XM_017600055.2

9225

XP_017455544.1

2207

transcript variant X1

isoform X1

XM_017600060.2

9165

XP_017455549.1

2187

transcript variant X7

isoform X7

XM_017600062.2

9141

XP_017455551.1

2179

transcript variant X10

isoform X10

XM_017600056.2

9225

XP_017455545.1

2207

transcript variant X2

isoform X2

XM_006252595.4

6869

XP_006252657.1

2144

transcript variant X13

isoform X13

XM_006252590.4

6974

XP_006252652.1

2179

transcript variant X8

isoform X8

XM_006252597.4

6842

XP_006252659.1

2135

transcript variant X15

isoform X15

XM_006252594.4

6914

XP_006252656.1

2159

transcript variant X12

isoform X12

XM_017600066.2

5814

XP_017455555.1

1741

transcript variant X16

isoform X16

XM_039094435.1

4850

XP_038950363.1

1355

transcript variant X20

isoform X17

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Post-Translational Modifications

PTM

Position

Type

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Structure

Cav1.3 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	9910.44	source
Mouse	10681.76	source
Rat	9629.42	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Kinetics

Cav1.3 have a hyperpolarized activation curve and fast (submillisecond) activation rise times. [506]

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Expression and Distribution

Cav1.3 can be found in auditory sensory hair cells, [505], neuronal cells and some epithelial cells [228]. In particular in the chick auditory papilla [507], frog saccule [508], trout saccule and mammalian cochlea [509], [510], [506].

Only L-type channels are present in turtle auditory hair cells. [228]

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CNS Sub-cellular Distribution

Calcium channels are clustered at synaptic release sites.[505]

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Function

Calcium channels are fundamental to signal processing in auditory sensory hair cells [511], regulating both the membrane excitability and neurotransmitter release [505].

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Interaction

Dihydropyridine

All L-type voltage gated Ca channels are characterized by high sensitivity to dihydropyridine (DHP) Ca2+ channel modulators, although differences in their voltage-dependence of DHP block exist [511].

L-type Dihydropyridine Antagonists

Cav1.3 is insensitive to the L-type dihydropyridine antagonists. [506]

Nifedipine and Bay K 8644

Nifedipine and Bay K 8644, respectively, block Cav1.3 channels. [230]

References

228

Schnee ME et al. Biophysical and pharmacological characterization of voltage-gated calcium currents in turtle auditory hair cells.
J. Physiol. (Lond.), 2003 Jun 15 , 549 (697-717).

229

Biophysical properties of CaV1.3 calcium channels in gerbil inner hair cells.
J. Physiol. (Lond.), 2008 Feb 15 , 586 (1029-42).

230

Michna M et al. Cav1.3 (alpha1D) Ca2+ currents in neonatal outer hair cells of mice.
J. Physiol. (Lond.), 2003 Dec 15 , 553 (747-58).

498

Catterall WA et al. International Union of Pharmacology. XL. Compendium of voltage-gated ion channels: calcium channels.
Pharmacol. Rev., 2003 Dec , 55 (579-81).

505

Roberts WM et al. Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells.
J. Neurosci., 1990 Nov , 10 (3664-84).

506

Koschak A et al. alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages.
J. Biol. Chem., 2001 Jun 22 , 276 (22100-6).

507

Kollmar R et al. Predominance of the alpha1D subunit in L-type voltage-gated Ca2+ channels of hair cells in the chicken's cochlea.
Proc. Natl. Acad. Sci. U.S.A., 1997 Dec 23 , 94 (14883-8).

508

Rodriguez-Contreras A et al. Direct measurement of single-channel Ca(2+) currents in bullfrog hair cells reveals two distinct channel subtypes.
J. Physiol. (Lond.), 2001 Aug 1 , 534 (669-89).

509

Zhang SY et al. Role of L-type Ca(2+) channels in transmitter release from mammalian inner hair cells I. Gross sound-evoked potentials.
J. Neurophysiol., 1999 Dec , 82 (3307-15).

510

Platzer J et al. Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels.
Cell, 2000 Jul 7 , 102 (89-97).

511

Striessnig J et al. L-type Ca2+ channels in Ca2+ channelopathies.
Biochem. Biophys. Res. Commun., 2004 Oct 1 , 322 (1341-6).

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Credits

Contributors: Rajnish Ranjan, Michael Schartner

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/81/ , accessed on 2024 Apr 26

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