Channelpedia

Cav3.3

Description: calcium channel, voltage-dependent, T type, alpha 1I subunit
Gene: Cacna1i
Alias: cacna1i, cav3.3, ca3.3, Ca(v)3.3

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Introduction

CACNA1I (also known as Cav3.3; KIAA1120) encodes Cav3.3, a T type LVA calcium channel found in neurons which is also know as a1I. Voltage-dependent calcium channels control the rapid entry of Ca(2+) into a variety of cell types and are therefore involved in both electrical and cellular signaling. T-type channels, such as CACNA1I, are activated by small membrane depolarizations and can generate burst firing and pacemaker activity

http://www.ncbi.nlm.nih.gov/gene/8911

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Gene

Species	NCBI gene ID	Chromosome	Position
Human	8911	22	118982
Mouse	239556	15	111054
Rat	56827	7	111422

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_021096.4	10002
Mouse	NM_001044308.2	9833
Rat	NM_020084.3	6709

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	Q9P0X4	2223
Mouse	E9Q7P2	2199
Rat	Q9Z0Y8	2201

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_021096.4

10002

NP_066919.2

2223

transcript variant 1

isoform a

NM_001003406.2

9897

NP_001003406.1

2188

transcript variant 2

isoform b

Predicted

XM_017029035.3

13276

XP_016884524.1

1606

transcript variant X1

isoform X1

XM_017029036.2

13273

XP_016884525.1

1605

transcript variant X2

isoform X2

XM_054326079.1

13303

XP_054182054.1

1605

transcript variant X2

isoform X2

XM_054326078.1

10191

XP_054182053.1

1606

transcript variant X1

isoform X1

Known

NM_001044308.2

9833

NP_001037773.2

2199

Predicted

XM_006520949.2

9859

XP_006521012.1

2226

transcript variant X1

isoform X1

XM_006520950.3

9820

XP_006521013.1

2213

transcript variant X2

isoform X2

XM_030248558.2

9739

XP_030104418.1

2186

transcript variant X3

isoform X3

Known

NM_020084.3

6709

NP_064469.3

2201

Predicted

XM_039079796.1

9739

XP_038935724.1

2213

transcript variant X2

isoform X2

XM_039079795.1

9777

XP_038935723.1

2226

transcript variant X1

isoform X1

XM_039079797.1

9696

XP_038935725.1

2199

transcript variant X3

isoform X3

XM_039079798.1

9657

XP_038935726.1

2186

transcript variant X4

isoform X4

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Post-Translational Modifications

PTM

Position

Type

Modified residue

1058

Phosphoserine

Glycosylation

173

N-linked (GlcNAc...) asparagine

Glycosylation

244

N-linked (GlcNAc...) asparagine

Glycosylation

311

N-linked (GlcNAc...) asparagine

Glycosylation

1342

N-linked (GlcNAc...) asparagine

Glycosylation

1345

N-linked (GlcNAc...) asparagine

Modified residue

1017

Phosphoserine

Glycosylation

171

N-linked (GlcNAc...) asparagine

Glycosylation

242

N-linked (GlcNAc...) asparagine

Glycosylation

309

N-linked (GlcNAc...) asparagine

Glycosylation

1301

N-linked (GlcNAc...) asparagine

Glycosylation

1304

N-linked (GlcNAc...) asparagine

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Structure

Cav3.3 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	9798.13	source
Mouse	9959.28	source
Rat	10633.19	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Kinetics

T-type channels are distinguished from high voltage-activated (HVA)1 Ca2+ channels by their unique biophysical properties, including low voltage activation, fast activation and inactivation kinetics that produce a criss-crossing pattern between successive traces of a current-voltage (IV) protocol, slow deactivation kinetics, and tiny single channel conductance (Perez-Reyes [528], Armstrong [1237], Carbone [1238], Randall [340]).

Expression studies found that Cav3.3 channels generate currents with much slower activation and inactivation kinetics than Cav3.1 and Cav3.2 channels, which show the more typical transient kinetics described for native T-type channels (Perez-Reyes [528], Perez-Reyes [1239], Cribbs [1240], Lee [1241]).

Cav3.1 and Cav3.2 channels are activating and inactivating much faster than Cav3.3 channels. (Park [113])

The kinetics of T-type channels resemble those of Na+ channels, albeit on a slower time scale, suggesting that they may also inactivate by a ball-and-chain mechanism. However, preliminary evidence indicates that T-type channels inactivate by similar processes as HVA Ca2+ channels.Multiple structural elements contribute to the slow kinetics of Cav3.3 channels. (Park [113])

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Biophysics

Model Cav3.3 (ID=42)

Animal	CH
CellType	CHO
Age	0 Days
Temperature	0.0°C
Reversal	30.0 mV
Ion	Ca +
Ligand ion
Reference	[103] Achraf Traboulsie et. al; J. Physiol. (Lond.) 2007 Jan 1
mpower	1.0
m Inf	1/(1+exp((v- -45.454426)/-5.073015))
m Tau	3.394938 +( 54.187616 / (1 + exp((v - -40.040397)/4.110392)))
hpower	1.0
h Inf	1 /(1+exp((v-(-74.031965))/8.416382))
h Tau	109.701136 + (0.003816 * exp(-v/4.781719))

MOD - xml - channelML

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CNS Sub-cellular Distribution

T-type Ca2+ currents are central determinants of neuronal excitability that are present in the somatodendritic compartment of many types of neurones (Carbone & Lux, 1984 [1238]; Talley et al. 1999 [1242]).

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Function

Genetic and pharmacological inhibition of T-type Ca2+ currents has demonstrated the importance of these currents in various sensory systems, ranging from pain perception and hyperalgesia (Kim et al. 2003 [1243]; Ikeda et al. 2003 [1244]), mechanoreceptor function (Shin et al. 2003 [1245]) and to olfaction (Kawai & Miyachi, 2001 [1246]).

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Interaction

Zinc

CaV 3.2 current (IC50 , 0.8 μM) is significantly more sensitive to Zn2 + than are CaV 3.1 and CaV 3.3 currents (IC50 , 80 μM and ∼160 μM, respectively). This inhibition of CaV 3 currents is associated with a shift to more negative membrane potentials of both steady-state inactivation for CaV 3.1, CaV 3.2 and CaV 3.3 and steady-state activation for CaV 3.1 and CaV 3.3 currents. We also document changes in kinetics, especially a significant slowing of the inactivation kinetics for CaV 3.1 and CaV 3.3, but not for CaV 3.2 currents. (Traboulsie [103])

Phorbol-12-myristate-13-acetate (PMA)

PMA augmented the current amplitudes of the three T-type channel isoforms (Cav3.1, Cav3.2, Cav3.3), but the fold stimulations and time courses differed. (Park [112])

References

Traboulsie A et al. Subunit-specific modulation of T-type calcium channels by zinc.
J. Physiol. (Lond.), 2007 Jan 1 , 578 (159-71).

Park JY et al. Activation of protein kinase C augments T-type Ca2+ channel activity without changing channel surface density.
J. Physiol. (Lond.), 2006 Dec 1 , 577 (513-23).

Park JY et al. Multiple structural elements contribute to the slow kinetics of the Cav3.3 T-type channel.
J. Biol. Chem., 2004 May 21 , 279 (21707-13).

T-type Ca2+ channels encode prior neuronal activity as modulated recovery rates.
J. Physiol. (Lond.), 2006 Mar 15 , 571 (519-36).

Cataldi M et al. Zn(2+) slows down Ca(V)3.3 gating kinetics: implications for thalamocortical activity.
J. Neurophysiol., 2007 Oct , 98 (2274-84).

Kovacs K et al. Subcellular distribution of low-voltage activated T-type Ca2+ channel subunits (Ca(v)3.1 and Ca(v)3.3) in reticular thalamic neurons of the cat.
J. Neurosci. Res., 2010 Feb 1 , 88 (448-60).

Randall AD et al. Contrasting biophysical and pharmacological properties of T-type and R-type calcium channels.
Neuropharmacology, 1997 Jul , 36 (879-93).

Perez-Reyes E Molecular physiology of low-voltage-activated t-type calcium channels.
Physiol. Rev., 2003 Jan , 83 (117-61).

Armstrong CM et al. Two distinct populations of calcium channels in a clonal line of pituitary cells.
Science, 1985 Jan 4 , 227 (65-7).

Carbone E et al. A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones.
Nature, 1984 Aug 9-15 , 310 (501-2).

Perez-Reyes E et al. Molecular characterization of a neuronal low-voltage-activated T-type calcium channel.
Nature, 1998 Feb 26 , 391 (896-900).

Cribbs LL et al. Cloning and characterization of alpha1H from human heart, a member of the T-type Ca2+ channel gene family.
Circ. Res., 1998 Jul 13 , 83 (103-9).

Lee JH et al. Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family.
J. Neurosci., 1999 Mar 15 , 19 (1912-21).

Talley EM et al. Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels.
J. Neurosci., 1999 Mar 15 , 19 (1895-911).

Kim D et al. Thalamic control of visceral nociception mediated by T-type Ca2+ channels.
Science, 2003 Oct 3 , 302 (117-9).

Ikeda H et al. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia.
Science, 2003 Feb 21 , 299 (1237-40).

Shin JB et al. A T-type calcium channel required for normal function of a mammalian mechanoreceptor.
Nat. Neurosci., 2003 Jul , 6 (724-30).

Kawai F et al. Enhancement by T-type Ca2+ currents of odor sensitivity in olfactory receptor cells.
J. Neurosci., 2001 May 15 , 21 (RC144).

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Credits

Contributors: Rajnish Ranjan, Michael Schartner

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/87/ , accessed on 2024 Apr 27

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