Affinage

CACNA1D

Voltage-dependent L-type calcium channel subunit alpha-1D · UniProt Q01668

Length
2161 aa
Mass
245.1 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CACNA1D encodes CaV1.3, the pore-forming α1 subunit of a low-voltage-activating L-type Ca²⁺ channel that opens at uniquely negative potentials (~-45 mV) and inactivates slowly, requiring co-assembly with auxiliary β and α2δ subunits for functional surface expression (PMID:11285265, PMID:7760845, PMID:27798183). A central determinant of its gating is its alternatively spliced C-terminus: a C-terminal modulatory domain (CTM) engages in an intramolecular interaction that weakens coupling of voltage-sensor charge movement to pore opening and tunes calmodulin-dependent inactivation, so that short variants lacking the CTM activate at more negative voltages and show enhanced Ca²⁺-dependent inactivation (PMID:18482979, PMID:24703308, PMID:21998309). Channel output is further shaped by ADAR-mediated RNA editing of the IQ domain, which weakens apoCaM pre-association to make CDI continuously tunable (PMID:24120865, PMID:29733375), and by signaling: PKA increases current (PMID:15615842), PKC phosphorylation at S81 decreases it (PMID:16973824), and an IGF-1/PLC/IP3/CaMKII pathway phosphorylates S1486 to potentiate the channel and drive CREB signaling (PMID:16763033), with CaMKII/densin conferring Ca²⁺-dependent facilitation (PMID:20392935). CaV1.3 assembles into cell-type-specific macromolecular complexes: postsynaptically its C-terminal PDZ-binding and proline-rich motifs bind Shank PDZ and SH3 domains for synaptic clustering and pCREB signaling (PMID:15689539, PMID:15689540), and it couples to RyR2 (PMID:17823125) and GABABR2 (PMID:20627102); at inner-hair-cell ribbon synapses it clusters at active zones under control of RIM2 and harmonin scaffolds and physically engages otoferlin (PMID:26034270, PMID:21822269, PMID:23613530, PMID:19004828). Functionally, CaV1.3 triggers RyR-dependent Ca²⁺ release to drive sinoatrial node diastolic depolarization and pacemaking (PMID:12700358, PMID:26786159), and mediates nanodomain Ca²⁺ control of ribbon-synapse exocytosis and maturation in cochlear hair cells (PMID:16354915, PMID:14645476, PMID:23197719). Loss-of-function mutation causes SANDD syndrome (sinoatrial node dysfunction and deafness) (PMID:21131953), whereas gain-of-function mutations in pore and gating residues cause primary aldosteronism with neuromuscular features and are found in autism spectrum disorder (PMID:23913001, PMID:25620733, PMID:31921405).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1995 Medium

    Established that the CACNA1D α1 subunit is non-functional alone and requires an auxiliary β subunit to form L-type current, defining the channel as a multi-subunit complex.

    Evidence Stable expression of α1 ± β2 in CHO cells with voltage-clamp; RT-PCR of pancreatic islets

    PMID:7760845

    Open questions at the time
    • Did not resolve native subunit stoichiometry
    • Splice-variant–specific gating not characterized
  2. 2001 High

    Defined the biophysical signature distinguishing CaV1.3 from CaV1.2 — activation at negative voltages, slow inactivation, and voltage-dependent rather than affinity-based low DHP sensitivity — and showed exon 8A is required for functional expression.

    Evidence Whole-cell patch-clamp of cloned human α1D splice variants in tsA-201 cells plus radioligand binding

    PMID:11285265

    Open questions at the time
    • Did not address in vivo physiological role
    • Structural basis of negative-voltage activation unresolved
  3. 2001 Medium

    Showed neuroendocrine CaV1.3 is stimulated rather than inhibited by Gi/Go-coupled GPCRs via a PKC-dependent mechanism, distinguishing its GPCR modulation from CaV2.2.

    Evidence Xenopus oocyte expression with voltage-clamp and pharmacological inhibitors

    PMID:11435619

    Open questions at the time
    • Phosphorylation site not mapped here
    • Native cell relevance untested
  4. 2003 High

    Genetic knockout established CaV1.3 as essential for cardiac pacemaking and for cochlear inner hair cell maturation and exocytosis, linking the channel to two distinct physiological systems.

    Evidence Cav1.3 KO mice; SAN and IHC patch-clamp; caged-Ca²⁺ photolysis; developmental immunohistochemistry

    PMID:12700358 PMID:14645476

    Open questions at the time
    • Downstream effectors of pacemaking not yet defined
    • Molecular basis of IHC maturation requirement unclear
  5. 2005 High

    Resolved how CaV1.3 is anchored and clustered at synapses, showing its C-terminal PDZ-binding and proline-rich motifs bind Shank PDZ and SH3 domains and are required for synaptic clustering, GPCR modulation, and pCREB signaling.

    Evidence Yeast two-hybrid, GST pull-down, neuronal expression with dominant-negative peptides and DHP-resistant mutants; patch-clamp with PDZ-competing peptides and CaV1.3 KO

    PMID:15689539 PMID:15689540

    Open questions at the time
    • Stoichiometry of the CaV1.3–Shank–Homer complex unresolved
    • Whether clustering requires additional scaffolds untested
  6. 2005 High

    Demonstrated nanodomain Ca²⁺ control of hair-cell exocytosis, with ~80 CaV1.3 channels per ribbon active zone and a few nearby channels gating vesicle release.

    Evidence Nonstationary fluctuation analysis, immunohistochemistry, and capacitance recordings in IHCs

    PMID:16354915

    Open questions at the time
    • Physical channel–vesicle tethering molecules not identified here
    • Active-zone architecture not resolved
  7. 2006 High

    Identified bidirectional kinase control of CaV1.3 — PKA increases current while PKC phosphorylation at N-terminal S81 (isozyme-selective) decreases it.

    Evidence Heterologous patch-clamp with 8-Br-cAMP/PKI, S81D phosphomimetic, competing peptide, and isozyme-selective PKC activators; phospho-Western blot

    PMID:15615842 PMID:16973824

    Open questions at the time
    • PKA phosphoacceptor residue not precisely mapped
    • In vivo physiological context of S81 regulation untested
  8. 2006 High

    Defined an IGF-1/PLC/IP3/CaMKII signaling cascade that phosphorylates EF-hand residue S1486 to potentiate CaV1.3 and drive CREB phosphorylation, linking channel modulation to gene expression.

    Evidence S1486A mutagenesis, pathway pharmacology, patch-clamp, and pCREB immunofluorescence in neurons

    PMID:16763033

    Open questions at the time
    • Direct CaMKII–S1486 phosphorylation not biochemically confirmed
    • Endogenous trigger in vivo undefined
  9. 2007 Medium

    Established physical and functional coupling of CaV1.3 to RyR2 and to CaBP1, connecting the channel to intracellular Ca²⁺ release and to anomalous inactivation control.

    Evidence Yeast two-hybrid, co-IP from hippocampus, siRNA knockdown; patch-clamp in IHCs and transfected cells with CaBP1

    PMID:17823125 PMID:17947313

    Open questions at the time
    • RyR2 interaction not reconstituted in vitro
    • Direct CaBP1 binding site mapping incomplete
  10. 2008 High

    Identified the C-terminal modulatory domain (CTM) as an intramolecular regulator of gating and CaM binding, generated by alternative splicing of the C-terminus.

    Evidence Patch-clamp of truncations, CTM-peptide rescue, and FRET in HEK-293 cells

    PMID:18482979

    Open questions at the time
    • Atomic structure of the CTM interaction unresolved
    • In vivo isoform ratios not quantified here
  11. 2008 Medium

    Showed otoferlin binds the CaV1.3 II-III loop in a Ca²⁺-dependent manner and that a DFNB9 mutation disrupts this, linking the channel to hair-cell synaptic vesicle machinery.

    Evidence GST pull-down with DFNB9 fusion proteins and Kd determination

    PMID:19004828

    Open questions at the time
    • Interaction not validated in native IHCs
    • Functional consequence on exocytosis inferred, not measured
  12. 2009 Medium

    Placed CaV1.3 in the retinal Usher protein network by demonstrating whirlin binding to its C-terminal PDZ motif and co-localization at photoreceptor cilium and synapse.

    Evidence Yeast two-hybrid, GST pull-down, co-IP, immuno-EM in retina

    PMID:19959638

    Open questions at the time
    • Functional role of CaV1.3 in photoreceptors not established
    • Single-lab interaction data
  13. 2010 High

    Connected CaV1.3 to human disease for the first time, showing a loss-of-function insertion causes non-conducting channels and SANDD syndrome matching the KO mouse.

    Evidence Positional cloning with heterologous expression and patch-clamp of mutant channel

    PMID:21131953

    Open questions at the time
    • Limited number of affected families
    • Tissue-specific severity determinants unclear
  14. 2010 High

    Defined complexes conferring facilitation and active-zone properties: densin/CaMKII enables Ca²⁺-dependent facilitation, and RIM proteins binding the β-subunit slow inactivation to generate the IHC window current.

    Evidence Co-IP from brain, HEK293 reconstitution, dominant-negative CaMKII, domain mapping; tsA-201 patch-clamp with RIM co-localization

    PMID:20363327 PMID:20392935

    Open questions at the time
    • RIM–CaV1.3 contact is indirect (via β-subunit)
    • In vivo facilitation contribution not quantified
  15. 2011 High

    Established harmonin as a dual regulator that limits CaV1.3 availability via ubiquitin-dependent degradation and, through dCT binding, enhances voltage-dependent facilitation and synchronous IHC exocytosis.

    Evidence Co-IP, IHC immunolocalization, ubiquitin pathway assays; patch-clamp and capacitance in dfcr mutant IHCs with domain deletion

    PMID:21822269 PMID:23613530

    Open questions at the time
    • E3 ligase mediating degradation not identified
    • Balance between degradation and facilitation roles unresolved
  16. 2011 Medium

    Mapped how alternative splicing at multiple C-terminal loci tunes inactivation, expanding the repertoire of functionally distinct CaV1.3 isoforms.

    Evidence Transcript-scanning, splice-variant antibodies, and patch-clamp of each HEK-expressed variant

    PMID:21998309

    Open questions at the time
    • Tissue distribution of each variant incompletely defined
    • Physiological role of individual variants untested
  17. 2013 High

    Defined CaV1.3 gain-of-function disease mechanism, showing somatic and germline mutations at Gly403/Ile770 shift activation and impair inactivation to cause aldosterone-producing adenomas and primary aldosteronism with neuromuscular features.

    Evidence Mutation identification with heterologous electrophysiology

    PMID:23913001

    Open questions at the time
    • Mechanism linking Ca²⁺ influx to aldosterone production not detailed
    • Neuromuscular phenotype mechanism unclear
  18. 2013 High

    Revealed RNA editing as a post-transcriptional tuner of CDI, acting by weakening apoCaM pre-binding rather than Ca²⁺/CaM binding, making inactivation responsive to ambient CaM.

    Evidence Electrophysiology of edited vs unedited channels with CaM binding assays in HEK cells and substantia nigra neurons

    PMID:24120865

    Open questions at the time
    • In vivo editing levels across tissues not mapped here
    • Functional consequence for neuronal excitability not directly tested
  19. 2013 Medium

    Identified a CaV1.3–GABABR2 interaction in which GABAB activation selectively increases CaV1.3 current, defining a receptor–channel signaling unit.

    Evidence Yeast two-hybrid, GST pull-down, co-IP, co-localization, patch-clamp, and Ca²⁺ imaging

    PMID:20627102

    Open questions at the time
    • Native physiological context untested
    • Single-lab data
  20. 2014 Medium

    Extended CaV1.3 gain-of-function disease to autism spectrum disorder via de novo mutations enhancing Ca²⁺ influx, and uncovered opposing CDI/VDI effects of one autism allele.

    Evidence Patch-clamp of patient-derived mutant channels in tsA-201/HEK cells with allosteric gating modeling

    PMID:25620733 PMID:27255217

    Open questions at the time
    • Neuronal/behavioral consequences not modeled in vivo
    • Single-lab electrophysiology
  21. 2014 Medium

    Demonstrated a non-canonical role: the CaV1.3 C-terminal domain translocates to the nucleus in a Ca²⁺-dependent manner to act as a transcriptional regulator of SK2 channel expression.

    Evidence CaV1.3 null mice, nuclear fractionation, reporter assays, and co-IP

    PMID:25538241

    Open questions at the time
    • DNA-binding partners of the C-terminal fragment unknown
    • Cleavage mechanism generating the fragment undefined
  22. 2014 High

    Defined the CTM mechanistically as a regulator of voltage-sensor-to-gate coupling, and showed CaV1.3 in dopamine neurons supports homeostatic D2-autoreceptor tuning via an NCS-1/GIRK2 network.

    Evidence Simultaneous gating- and ionic-current measurements of splice variants; brain-slice electrophysiology with genetic/pharmacological tools

    PMID:24703308 PMID:24934288

    Open questions at the time
    • Structural basis of CTM-mediated coupling unresolved
    • Direct CaV1.3–NCS-1 contact not demonstrated
  23. 2015 High

    Confirmed in vivo, cell-type-specific CTM function and that RIM2 promotes synaptic CaV1.3 channel abundance required for sound-onset encoding.

    Evidence CTM-tagged knockin mice with IHC/chromaffin patch-clamp; hair-cell-specific RIM2 deletion with superresolution microscopy, Ca²⁺ imaging, and electron tomography

    PMID:26034270 PMID:26379493

    Open questions at the time
    • Mechanism of RIM2-dependent channel recruitment incompletely defined
    • CTM regulation in other cell types untested
  24. 2016 High

    Established that CaV1.3 triggers and synchronizes RyR-dependent local Ca²⁺ release to control sinoatrial automaticity, with caffeine-induced CICR rescuing pacemaking in KO cells.

    Evidence Ca²⁺ imaging and AP-clamp in Cav1.3-/- SAN cells and ex vivo preparations with functional rescue

    PMID:26786159

    Open questions at the time
    • Spatial relationship of CaV1.3 to RyR in SAN not directly imaged
    • Quantitative contribution vs. surface-membrane clock unresolved
  25. 2016 High

    Showed the α2δ subunit co-assembles with CaV1.3 at IHC presynapses, supporting current amplitude, gating, exocytosis, and trans-synaptic alignment with postsynaptic AMPA receptors.

    Evidence Patch-clamp, exocytosis measurements, immunofluorescence, and ABR in α2δ2-null (ducky) mice

    PMID:27798183

    Open questions at the time
    • Molecular basis of trans-synaptic alignment unclear
    • Whether α2δ directly mediates clustering untested
  26. 2017 Medium

    Extended the gain-of-function disease spectrum with activation-gate mutation V401L producing enhanced current and hyperpolarized gating in both splice backgrounds while retaining isradipine sensitivity.

    Evidence Whole-cell patch-clamp of mutant channel complexes in tsA-201 cells

    PMID:28472301

    Open questions at the time
    • In vivo consequence not modeled
    • Single-lab data
  27. 2018 Medium

    Defined the molecular basis of tissue-selective IQ-domain editing, showing an exon41–intron RNA duplex (ECS) and SRSF9 control ADAR2 access, with neuronal SRSF9 down-regulation enabling neuron-specific editing.

    Evidence Minigene assays with ADAR2, SRSF9 overexpression/knockdown, RNA–protein interaction assays, and evolutionary analysis

    PMID:29733375

    Open questions at the time
    • In vivo editing regulation by SRSF9 not confirmed
    • Other splice-editing crosstalk loci untested
  28. 2020 Medium

    Distinguished gain- versus loss-of-function as the disease determinant at residue S652, showing only the hyperpolarizing GOF variant (S652L) increases window currents and Ca²⁺ load and confers high disease risk.

    Evidence Comparative whole-cell patch-clamp of S652L vs S652W mutant channel complexes in tsA-201 cells

    PMID:31921405

    Open questions at the time
    • Genotype–phenotype correlation across patients incomplete
    • Therapeutic relevance of increased isradipine sensitivity untested in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CaV1.3 macromolecular complexes are assembled and spatially organized into cell-type-specific signaling units (cardiac, cochlear, neuronal), and the structural basis of CTM-mediated gating and CaM/editing tuning, remain to be resolved.
  • No atomic structure of CaV1.3 with its scaffolds/auxiliary subunits in the corpus
  • Mechanism generating and targeting the nuclear C-terminal fragment unknown
  • In vivo integration of kinase, editing, and splicing regulation not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0060089 molecular transducer activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 1 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 3 R-HSA-397014 Muscle contraction 2
Partners
CABP1GABBR2OTOFRIMS2RYR2SHANKUSH1CWHRN
Complex memberships
CaV1.3 L-type channel (α1D/β/α2δ)CaV1.3–densin–CaMKII complexIHC ribbon-synapse active zone (CaV1.3–RIM2–harmonin)postsynaptic density CaV1.3–Shank–Homer complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CaV1.3 (α1D) subunits form L-type Ca²⁺ channels that activate at more negative voltages (threshold ~-45.7 mV) and inactivate more slowly than α1C channels; the exon 8A splice variant is required for functional expression, while exon 8B yields no intact protein or current. Radioligand binding showed lower DHP sensitivity is due to voltage-dependence of DHP block rather than reduced affinity for the DHP binding pocket. Whole-cell patch-clamp of tsA-201 cells expressing cloned human α1D splice variants; radioligand binding experiments The Journal of biological chemistry High 11285265
2003 Genetic inactivation of Cav1.3 in mice significantly slows sinoatrial node (SAN) pacemaker activity and promotes spontaneous arrhythmia; Cav1.3 contributes a major component of L-type current (ICa,L) activating at negative voltages corresponding to the diastolic depolarization range, demonstrating its essential role in cardiac pacemaking. Gene-targeted knockout mice; patch-clamp recording of SAN cells; pharmacological dissection of ICa,L Proceedings of the National Academy of Sciences of the United States of America High 12700358
2003 CaV1.3 channels are essential for cochlear inner hair cell (IHC) development and synaptic transmission: CaV1.3-/- IHCs lack Ca²⁺ action potentials, show only marginal depolarization-induced exocytosis (proportional to the residual Ca²⁺ current), retain efferent cholinergic synaptic input beyond normal developmental window, and fail to acquire large-conductance Ca²⁺-activated K⁺ channels, indicating CaV1.3 is required for normal IHC maturation. Patch-clamp recordings in CaV1.3-/- mouse IHCs; photolysis of caged Ca²⁺; developmental immunohistochemistry The Journal of neuroscience : the official journal of the Society for Neuroscience High 14645476
2005 CaV1.3 channels are concentrated at ribbon-type active zones of IHCs (~80 channels per active zone); exocytosis of the readily releasable vesicle pool shows near-unity apparent Ca²⁺ cooperativity when open-channel number is manipulated but high intrinsic cooperativity when single-channel current is varied, indicating nanodomain Ca²⁺ control of exocytosis by few nearby CaV1.3 channels. Nonstationary fluctuation analysis; immunohistochemistry; membrane capacitance recordings with pharmacological manipulation of Ca²⁺ current The Journal of neuroscience : the official journal of the Society for Neuroscience High 16354915
2005 D2 dopaminergic and M1 muscarinic GPCR modulation of CaV1.3 channels in striatal medium spiny neurons depends on a Shank-binding PDZ domain in the CaV1.3 C-terminus; disruption of the CaV1.3 PDZ–Shank interaction or the Shank–Homer interaction abolishes this GPCR modulation. Shank colocalized with CaV1.3a at spine-like puncta co-expressing PSD-95 and corticostriatal synaptic markers. Whole-cell patch-clamp; intracellular peptide dialysis to compete PDZ binding; genetic deletion of CaV1.3; immunohistochemistry The Journal of neuroscience : the official journal of the Society for Neuroscience High 15689540
2005 CaV1.3a (long C-terminal splice variant) specifically associates with Shank via two distinct interactions: the C-terminal PDZ-binding motif binds the Shank PDZ domain, and the proline-rich region binds the Shank SH3 domain. Shank-binding motifs in CaV1.3a are necessary and sufficient for synaptic clustering of CaV1.3 channels and are required for pCREB signaling in hippocampal neurons. Yeast two-hybrid screen; in vitro GST pull-down; recombinant epitope-tagged CaV1.3 in hippocampal neurons; dominant-negative peptides; DHP-resistant CaV1.3 mutants The Journal of neuroscience : the official journal of the Society for Neuroscience High 15689539
2006 PKA phosphorylation of CaV1.3 α1D at a serine residue (confirmed by 8-Br-cAMP stimulation and PKI inhibition) significantly increases peak CaV1.3 Ca²⁺ current density, identifying PKA as a positive regulator of CaV1.3 channel activity in the sinoatrial node and atria. Heterologous expression in tsA201 cells; whole-cell patch-clamp; 8-Br-cAMP; PKA inhibitor PKI; Western blot phosphorylation assay American journal of physiology. Heart and circulatory physiology Medium 15615842
2006 PKC inhibits CaV1.3 Ca²⁺ channel activity through phosphorylation of serine 81 in the N-terminal domain; a S81D phosphomimetic mutation recapitulates PKC inhibition, a competing peptide spanning S81 prevents it, and only βII- and ε-PKC isozymes mediate this regulation. Site-directed mutagenesis (S81D); competing N-terminal peptide dialysis; isozyme-selective PKC activators; whole-cell patch-clamp in heterologous expression American journal of physiology. Heart and circulatory physiology High 16973824
2006 IGF-1 potentiates CaV1.3 channels via a signaling pathway requiring PLC, Ca²⁺ release from IP3-sensitive stores, and CaMKII phosphorylation of serine S1486 in the EF-hand motif of the CaV1.3 α1 subunit; this causes a left-shift in the I-V relationship and potentiates CREB phosphorylation. Site-directed mutagenesis (S1486A); pharmacological inhibitors of PLC, IP3R, CaMKII; whole-cell patch-clamp; pCREB immunofluorescence in cortical/hippocampal neurons The Journal of neuroscience : the official journal of the Society for Neuroscience High 16763033
2007 The N-terminus of CaV1.3 α1 subunit physically interacts with the N-terminal region of ryanodine receptor type 2 (RyR2); this complex is co-immunoprecipitated from hippocampal tissue, and CaV1.3 activation triggers RyR-dependent Ca²⁺ release and upregulates RyR2 mRNA; siRNA silencing of CaV1.3 blocks both acute and long-term effects on RyR. Yeast two-hybrid; co-immunoprecipitation from rat hippocampus; immunocytochemistry; siRNA knockdown; KCl depolarization assay; RT-PCR The Journal of biological chemistry Medium 17823125
2007 CaBP1, a Ca²⁺-binding protein, most efficiently suppresses Ca²⁺-dependent inactivation (CDI) of CaV1.3 channels in transfected cells by interacting with calmodulin-binding sequences in CaV1.3; CaBP1 is strongly localized at the presynaptic ribbon synapse of adult IHCs and is implicated in conferring the anomalously slow CDI of CaV1.3 currents required for auditory transmission. Whole-cell patch-clamp in transfected cells and IHCs from CaBP4-/- mice; immunolocalization; binding assay The Journal of physiology Medium 17947313
2008 Alternative splicing of the CaV1.3 C-terminus generates long (CaV1.3_42) and short (CaV1.3_42A) variants; the short form activates at more negative voltages and shows enhanced CDI. The last 116 aa of the C-terminus constitutes a C-terminal modulatory domain (CTM); co-expression of the CTM peptide reverts short-form gating. FRET experiments confirmed an intramolecular interaction within the C-terminus that also modulates calmodulin binding. Patch-clamp of HEK-293 cells; channel truncations; co-expression of CTM peptide; FRET experiments The Journal of biological chemistry High 18482979
2008 Otoferlin C2D domain binds the CaV1.3 II-III intracellular loop in a Ca²⁺-dependent manner; the DFNB9 deafness mutation L1011P in C2D renders this binding Ca²⁺-insensitive and greatly diminished, implicating CaV1.3–otoferlin interaction in regulation of hair cell synaptic exocytosis. GST pull-down with fusion proteins containing DFNB9 mutations; Ca²⁺-dependent binding assays; Kd determination The Journal of biological chemistry Medium 19004828
2010 Loss-of-function CACNA1D mutation (glycine insertion in a conserved alternatively spliced region near the channel pore) results in non-conducting CaV1.3 channels with abnormal voltage-dependent gating, causing SANDD syndrome (sinoatrial node dysfunction and deafness) in humans, closely resembling the Cacna1d-/- mouse phenotype. Positional cloning; heterologous expression of mutant channel with patch-clamp recordings Nature neuroscience High 21131953
2010 Densin is required for Ca²⁺-dependent facilitation of CaV1.3 channels: neither CaMKII nor densin alone affects CaV1.3, but together they augment CaV1.3 Ca²⁺ currents during repetitive stimuli; facilitation requires CaMKII activation and its association with densin, as well as densin binding to the CaV1.3 α1 subunit C-terminal domain. CaV1.3, densin, and CaMKII form a complex in brain. Co-immunoprecipitation from brain; transfection in HEK293T cells; patch-clamp; dominant-negative CaMKII; binding domain mapping The Journal of neuroscience : the official journal of the Society for Neuroscience High 20392935
2010 RIM2α protein co-localizes with CaV1.3 at the presynaptic compartment of cochlear IHCs; RIM proteins bind the β-subunit of the CaV1.3 channel complex and slow both Ca²⁺- and voltage-dependent inactivation, generating a non-inactivating window current characteristic of IHC CaV1.3 currents. Co-localization immunofluorescence; heterologous expression with patch-clamp in tsA-201 cells Molecular and cellular neurosciences Medium 20363327
2011 Harmonin, a scaffolding protein at the IHC presynapse, interacts with CaV1.3 and limits channel availability through a ubiquitin-dependent proteosomal degradation pathway. Co-immunoprecipitation; immunolocalization at IHC presynapse; ubiquitin pathway assay Nature neuroscience High 21822269
2011 Alternative splicing at four loci in the CaV1.3 C-terminus (exons 41, 43, 44, 48) modulates channel electrophysiological properties: splicing of exon 41 removes the IQ motif causing diminished inactivation; exon 43 splicing causes a frameshift with robust inactivation; exons 44 and 48 alter interaction of the distal modulator with the IQ domain, tapering inactivation. Transcript-scanning; splice-variant-specific antibodies for localization; patch-clamp of HEK cells expressing each variant The Journal of biological chemistry Medium 21998309
2012 Presynaptic CaV1.3 activity regulates synaptic ribbon size in zebrafish hair cells: genetic disruption or acute pharmacological block of CaV1.3a causes ribbon enlargement, while channel activation reduces ribbon size and the number of intact synapses. Ca²⁺ influx through CaV1.3 is required for synaptic maintenance (independent of neurotransmission). In vivo Ca²⁺ imaging; confocal and super-resolution microscopy; pharmacological block/activation; vglut3 mutant controls The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 23197719
2013 Somatic gain-of-function mutations at Gly403 (four variants) and Ile770 in CaV1.3 cause aldosterone-producing adenomas by shifting channel activation to less depolarized potentials; Gly403 alterations additionally impair channel inactivation. De novo germline mutations at identical positions cause primary aldosteronism with neuromuscular abnormalities. Somatic/germline mutation identification; electrophysiological characterization of mutant channels expressed in heterologous cells Nature genetics High 23913001
2013 RNA editing of the CaV1.3 IQ domain (by ADAR) reduces Ca²⁺-dependent inactivation (CDI) not by weakening Ca²⁺/CaM binding to the edited IQ domain, but by weakening the pre-binding of Ca²⁺-free CaM (apoCaM) to the channel, thereby making CDI continuously tunable by ambient CaM levels. Electrophysiology of edited vs. unedited CaV1.3 in HEK cells; CaM binding assays; experiments in substantia nigra neurons Cell reports High 24120865
2013 CaV1.3 α1D interacts with GABAB receptor subunit 2 (GABABR2): CaV1.3-NT associates with GABABR2-CT, they co-localize in HEK293 cells and hippocampal neurons, and GABABR activation selectively increases CaV1.3 currents and intracellular Ca²⁺ via CaV1.3 but not CaV1.2. Yeast two-hybrid; GST pull-down; co-immunoprecipitation; co-localization immunofluorescence; patch-clamp; Ca²⁺ imaging FEBS letters Medium 20627102
2013 Harmonin binding to the CaV1.3 α1 subunit distal C-terminus (dCT) enhances voltage-dependent facilitation (VDF) of CaV1.3 currents and promotes synchronous exocytosis in IHCs; the deaf-circler dfcr harmonin mutant, which does not interact with the α1.3 dCT, has reduced VDF and impaired synchronous exocytosis. Patch-clamp of HEK293T cells and mouse IHCs from dfcr mice; membrane capacitance recordings; domain deletion analysis The Journal of physiology Medium 23613530
2014 De novo CaV1.3 mutations p.A749G and p.G407R found in autism spectrum disorder patients cause gain-of-function: p.A749G shifts voltage dependence of activation and inactivation ~15 mV to more negative voltages; p.G407R markedly slows current inactivation. Both are compatible with enhanced Ca²⁺ influx. Whole-cell patch-clamp of tsA-201 cells expressing patient-derived mutant channel complexes Biological psychiatry Medium 25620733
2014 The C-terminal domain of CaV1.3 translocates to the nucleus in a Ca²⁺-dependent manner, where it functions as a transcriptional regulator modulating SK2 channel expression; ablation of CaV1.3 decreases myosin light chain 2 protein, which interacts with and increases membrane localization of SK2 channels. CaV1.3 null mutant mouse; nuclear fractionation; transcriptional reporter assays; co-immunoprecipitation The Journal of biological chemistry Medium 25538241
2014 The C-terminal modulatory domain (CTM) of CaV1.3 controls coupling efficiency between voltage-sensor charge movement and pore opening: short variants lacking the CTM show stronger coupling, shifting ICa-V ~7.2 mV negative without altering charge movement (QON-V), demonstrating the CTM weakens voltage-sensor-to-gate coupling. Whole-cell patch-clamp measuring both gating currents (QON-V) and ionic currents (ICa-V) in tsA-201 cells expressing long and short CaV1.3 splice variants Biophysical journal High 24703308
2015 RIM2α and RIM2β promote the abundance of CaV1.3 Ca²⁺ channels at inner hair cell active zones: RIM2α-deficient IHCs cluster fewer synaptic CaV1.3 channels (shown by superresolution microscopy), have reduced Ca²⁺ influx and reduced exocytosis proportional to Ca²⁺ current reduction, and impaired sound-onset encoding. Immunofluorescence; patch-clamp; fluctuation analysis; confocal Ca²⁺ imaging; electron tomography; superresolution microscopy; hair cell-specific RIM2 deletion Proceedings of the National Academy of Sciences of the United States of America High 26034270
2015 The CaV1.3 C-terminal automodulatory domain (CTM) functions in a cell-type-specific manner in vivo: CTM elimination impairs Ca²⁺-dependent inactivation in cochlear IHCs but increases it in chromaffin cells (reducing resting potential and pacemaking), while not affecting hearing thresholds. Biochemical evidence from CTM-tagged knockin mice confirms existence of long and short CaV1.3 α1-subunit isoforms in brain. Knockin mice with HA-tagged CTM (Cav1.3DCRD_HA/HA); patch-clamp of IHCs and chromaffin cells; Western blot; auditory brainstem responses Frontiers in cellular neuroscience High 26379493
2014 Cav1.3 L-type Ca²⁺ channel activity in substantia nigra dopamine neurons is required for homeostatic modulation of D2-autoreceptor responses: Cav1.3 activity, internal Ca²⁺, and neuronal calcium sensor NCS-1 interaction with D2-autoreceptors are required for expression of sensitized D2-AR phenotype; L-DOPA or cocaine induces adult-like non-desensitizing D2-AR responses via this Cav1.3/NCS-1/D2/GIRK2 signaling network. Electrophysiology in acute brain slices; pharmacological and genetic tools; mRNA analysis of human SN DA neurons Brain : a journal of neurology Medium 24934288
2016 Cav1.3 channels regulate ryanodine receptor-dependent Ca²⁺ release during SAN pacemaker activity: Cav1.3 deficiency reduces the frequency of local Ca²⁺ release events and prevents their synchronization; pacemaker activity in Cav1.3-/- SAN cells was rescued by caffeine-mediated stimulation of Ca²⁺-induced Ca²⁺ release, showing Cav1.3 triggers local Ca²⁺ release to control automaticity. Isolated SAN cells and ex vivo SAN preparations from Cav1.3-/- mice; Ca²⁺ imaging; action potential voltage-clamp commands Cardiovascular research High 26786159
2016 The α2δ2 auxiliary subunit co-assembles with CaV1.3 at IHC presynapses; loss of α2δ2 (ducky mouse) reduces CaV1.3-mediated Ca²⁺ currents by 30-40%, alters gating properties (activation voltage, voltage sensitivity), proportionally reduces exocytosis, and impairs trans-synaptic alignment of presynaptic CaV1.3 clusters with postsynaptic AMPA receptor clusters. Patch-clamp; exocytosis measurements; immunofluorescence; auditory brainstem responses in α2δ2-null mice The Journal of neuroscience : the official journal of the Society for Neuroscience High 27798183
2017 De novo CaV1.3 mutation V401L (in the activation gate) causes gain-of-function: enhanced current density, hyperpolarizing shift in activation and inactivation voltage dependence, reduced inactivation; effects present in both long and short C-terminal splice variants. Mutant channels retain full sensitivity to isradipine. Whole-cell patch-clamp in tsA-201 cells expressing mutant channel complexes Human molecular genetics Medium 28472301
2018 Tissue-selective RNA editing of CaV1.3 mRNA by ADAR2 at the IQ domain depends on a 40 bp RNA duplex between exon 41 and an evolutionarily conserved editing site complementary sequence (ECS) in the preceding intron; splicing factor SRSF9 potently inhibits this editing by direct RNA interaction, and selective down-regulation of SRSF9 in neurons provides the basis for neuron-specific CaV1.3 editing. Minigene expression with ADAR2 co-expression; SRSF9 overexpression/knockdown; RNA-protein interaction assay; evolutionary sequence analysis Nucleic acids research Medium 29733375
2016 Autism-associated mutation A760G (reported as A749G in patient) has opposing effects: it severely diminishes Ca²⁺-dependent inactivation (CDI) of CaV1.3 channels while simultaneously increasing voltage-dependent inactivation (VDI); the mechanism of CDI reduction involves enhanced channel opening within the Ca²⁺-inactivated mode, and the combined deficits are predicted to increase intracellular Ca²⁺. Whole-cell patch-clamp in HEK cells expressing mutant CaV1.3; allosteric model of channel gating Scientific reports Medium 27255217
2020 CACNA1D gain-of-function mutation S652L causes a ~13-17 mV hyperpolarizing shift in activation and inactivation, increases window currents at subthreshold voltages, slows tail currents, and increases Ca²⁺ during AP-like stimulations; a corresponding S652W loss-of-function variant shifts parameters to more positive voltages, demonstrating that only gain-of-function variants confer high disease risk. S652L increases CaV1.3 sensitivity to isradipine 3-4-fold. Whole-cell patch-clamp of tsA-201 cells expressing mutant channel complexes; comparison of gain- vs. loss-of-function variants Molecular autism Medium 31921405
2009 Whirlin (USH2D protein) specifically interacts with CaV1.3 (α1D) C-terminal PDZ-binding motif; in adult photoreceptors, CaV1.3 and whirlin co-localize at the connecting cilium region and at the synapse, indicating CaV1.3 is a component of the Usher protein network in the retina. Yeast two-hybrid; GST pull-down; co-immunoprecipitation; immunofluorescence and immunoelectron microscopy in retina Investigative ophthalmology & visual science Medium 19959638
1995 CACNA1D (CACN4) requires co-expression with the β2-subunit for functional L-type Ca²⁺ channel expression; α1 subunit alone yields no current, whereas α1+β2 co-expression produces L-type currents in CHO cells. Multiple alternatively spliced variants are expressed in pancreatic islets. Stable expression in CHO cells; whole-cell voltage-clamp; RT-PCR of rat islets Molecular endocrinology (Baltimore, Md.) Medium 7760845
2001 The neuroendocrine CaV1.3 channel is stimulated (not inhibited) by ligand-bound Gi/Go-coupled GPCRs; this stimulation is mimicked by phorbol ester and blocked by serine/threonine kinase inhibitors but not by PI3K inhibitor wortmannin, indicating PKC-dependent GPCR stimulation of CaV1.3, distinct from the inhibitory Gi/Go modulation seen in CaV2.2 channels. Heterologous expression in Xenopus oocytes; whole-cell voltage-clamp; pharmacological inhibitors Molecular endocrinology (Baltimore, Md.) Medium 11435619

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nature genetics 475 23913001
2001 alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. The Journal of biological chemistry 371 11285265
2003 Functional role of L-type Cav1.3 Ca2+ channels in cardiac pacemaker activity. Proceedings of the National Academy of Sciences of the United States of America 368 12700358
2003 CaV1.3 channels are essential for development and presynaptic activity of cochlear inner hair cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 308 14645476
2005 Few CaV1.3 channels regulate the exocytosis of a synaptic vesicle at the hair cell ribbon synapse. The Journal of neuroscience : the official journal of the Society for Neuroscience 238 16354915
2010 Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness. Nature neuroscience 235 21131953
2005 G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domain. The Journal of neuroscience : the official journal of the Society for Neuroscience 217 15689540
2014 CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type calcium channels. Biological psychiatry 147 25620733
2012 CaV1.3-selective L-type calcium channel antagonists as potential new therapeutics for Parkinson's disease. Nature communications 140 23093183
2005 Association of CaV1.3 L-type calcium channels with Shank. The Journal of neuroscience : the official journal of the Society for Neuroscience 124 15689539
2014 The role of L-type voltage-gated calcium channels Cav1.2 and Cav1.3 in normal and pathological brain function. Cell and tissue research 123 24996399
2008 Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain. The Journal of biological chemistry 121 18482979
2005 Functional roles of Cav1.3(alpha1D) calcium channels in atria: insights gained from gene-targeted null mutant mice. Circulation 115 16172271
2003 Age-related working memory impairment is correlated with increases in the L-type calcium channel protein alpha1D (Cav1.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment. Brain research. Molecular brain research 113 12591156
2003 Cav1.3 (alpha1D) Ca2+ currents in neonatal outer hair cells of mice. The Journal of physiology 111 14514878
2014 Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons. Brain : a journal of neurology 102 24934288
2009 Elementary properties of CaV1.3 Ca(2+) channels expressed in mouse cochlear inner hair cells. The Journal of physiology 97 19917569
2007 Ca2+-binding proteins tune Ca2+-feedback to Cav1.3 channels in mouse auditory hair cells. The Journal of physiology 97 17947313
2017 New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy. Human molecular genetics 93 28472301
2012 Presynaptic CaV1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 92 23197719
2008 Direct interaction of otoferlin with syntaxin 1A, SNAP-25, and the L-type voltage-gated calcium channel Cav1.3. The Journal of biological chemistry 89 19004828
2006 Ca1.2 and CaV1.3 neuronal L-type calcium channels: differential targeting and signaling to pCREB. The European journal of neuroscience 88 16706838
2016 L-type Cav1.3 channels regulate ryanodine receptor-dependent Ca2+ release during sino-atrial node pacemaker activity. Cardiovascular research 81 26786159
2006 The L-Type voltage-gated calcium channel Cav1.3 mediates consolidation, but not extinction, of contextually conditioned fear in mice. Learning & memory (Cold Spring Harbor, N.Y.) 80 17015855
2011 Functional characterization of alternative splicing in the C terminus of L-type CaV1.3 channels. The Journal of biological chemistry 78 21998309
2001 Functional properties of Cav1.3 (alpha1D) L-type Ca2+ channel splice variants expressed by rat brain and neuroendocrine GH3 cells. The Journal of biological chemistry 77 11514547
2007 Functional interaction of neuronal Cav1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus. The Journal of biological chemistry 75 17823125
2010 Ca2+-dependent facilitation of Cav1.3 Ca2+ channels by densin and Ca2+/calmodulin-dependent protein kinase II. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 20392935
2017 A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. Pediatric diabetes 70 28318089
2016 Cav 1.3 (CACNA1D) L-type Ca2+ channel dysfunction in CNS disorders. The Journal of physiology 69 26842699
2001 Functional expression and characterization of a voltage-gated CaV1.3 (alpha1D) calcium channel subunit from an insulin-secreting cell line. Molecular endocrinology (Baltimore, Md.) 69 11435619
2012 The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes. Diabetologia 68 23229155
2011 Harmonin inhibits presynaptic Cav1.3 Ca²⁺ channels in mouse inner hair cells. Nature neuroscience 68 21822269
2015 Clinical and Steroidogenic Characteristics of Aldosterone-Producing Adenomas With ATPase or CACNA1D Gene Mutations. The Journal of clinical endocrinology and metabolism 65 26606680
1995 Molecular diversity and functional characterization of voltage-dependent calcium channels (CACN4) expressed in pancreatic beta-cells. Molecular endocrinology (Baltimore, Md.) 65 7760845
2005 Novel molecular mechanism involving alpha1D (Cav1.3) L-type calcium channel in autoimmune-associated sinus bradycardia. Circulation 64 15939813
2003 Neurological phenotype and synaptic function in mice lacking the CaV1.3 alpha subunit of neuronal L-type voltage-dependent Ca2+ channels. Neuroscience 63 12890513
2013 Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers. Urologic oncology 62 24054868
2007 Apical GLUT2 and Cav1.3: regulation of rat intestinal glucose and calcium absorption. The Journal of physiology 62 17272350
2006 Insulin-like growth factor-1 modulation of CaV1.3 calcium channels depends on Ca2+ release from IP3-sensitive stores and calcium/calmodulin kinase II phosphorylation of the alpha1 subunit EF hand. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 16763033
2006 Synaptic organization in cochlear inner hair cells deficient for the CaV1.3 (alpha1D) subunit of L-type Ca2+ channels. Neuroscience 59 16828974
2016 α2δ2 Controls the Function and Trans-Synaptic Coupling of Cav1.3 Channels in Mouse Inner Hair Cells and Is Essential for Normal Hearing. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 27798183
2008 Biophysical properties of CaV1.3 calcium channels in gerbil inner hair cells. The Journal of physiology 57 18174213
2003 Enhanced expression of L-type Cav1.3 calcium channels in murine embryonic hearts from Cav1.2-deficient mice. The Journal of biological chemistry 57 12900400
2020 De novo CACNA1D Ca2+ channelopathies: clinical phenotypes and molecular mechanism. Pflugers Archiv : European journal of physiology 55 32583268
2015 The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions. Cell calcium 55 26459417
2015 Rab3-interacting molecules 2α and 2β promote the abundance of voltage-gated CaV1.3 Ca2+ channels at hair cell active zones. Proceedings of the National Academy of Sciences of the United States of America 54 26034270
2012 Distinct localization and modulation of Cav1.2 and Cav1.3 L-type Ca2+ channels in mouse sinoatrial node. The Journal of physiology 52 23045342
2011 CaV1.3 channels and intracellular calcium mediate osmotic stress-induced N-terminal c-Jun kinase activation and disruption of tight junctions in Caco-2 CELL MONOLAYERS. The Journal of biological chemistry 51 21737448
2007 Voltage-dependent calcium channel CaV1.3 subunits regulate the light peak of the electroretinogram. Journal of neurophysiology 51 17376851
2014 Regulation of gene transcription by voltage-gated L-type calcium channel, Cav1.3. The Journal of biological chemistry 49 25538241
2022 tRF-Val-CAC-016 modulates the transduction of CACNA1d-mediated MAPK signaling pathways to suppress the proliferation of gastric carcinoma. Cell communication and signaling : CCS 48 35590368
2013 Continuously tunable Ca(2+) regulation of RNA-edited CaV1.3 channels. Cell reports 48 24120865
2009 Association of whirlin with Cav1.3 (alpha1D) channels in photoreceptors, defining a novel member of the usher protein network. Investigative ophthalmology & visual science 47 19959638
2004 Localization and modulation of {alpha}1D (Cav1.3) L-type Ca channel by protein kinase A. American journal of physiology. Heart and circulatory physiology 47 15615842
2016 Cav1.2 and Cav1.3 L-type calcium channels independently control short- and long-term sensitization to pain. The Journal of physiology 46 27231046
2007 Calcium absorption by Cav1.3 induces terminal web myosin II phosphorylation and apical GLUT2 insertion in rat intestine. The Journal of physiology 46 17272349
2015 Cell-type-specific tuning of Cav1.3 Ca(2+)-channels by a C-terminal automodulatory domain. Frontiers in cellular neuroscience 43 26379493
2010 Modulation of Cav1.3 Ca2+ channel gating by Rab3 interacting molecule. Molecular and cellular neurosciences 43 20363327
2020 Biophysical classification of a CACNA1D de novo mutation as a high-risk mutation for a severe neurodevelopmental disorder. Molecular autism 42 31921405
1995 The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes. Genomics 42 7557998
2013 Burst activity and ultrafast activation kinetics of CaV1.3 Ca²⁺ channels support presynaptic activity in adult gerbil hair cell ribbon synapses. The Journal of physiology 41 23713031
2017 Aldosterone-Producing Adenomas: Histopathology-Genotype Correlation and Identification of a Novel CACNA1D Mutation. Hypertension (Dallas, Tex. : 1979) 40 28584016
2015 Evaluation of genetic susceptibility of common variants in CACNA1D with schizophrenia in Han Chinese. Scientific reports 40 26255836
2004 Disturbed atrio-ventricular conduction and normal contractile function in isolated hearts from Cav1.3-knockout mice. Naunyn-Schmiedeberg's archives of pharmacology 40 15146309
2018 Identification of CACNA1D variants associated with sinoatrial node dysfunction and deafness in additional Pakistani families reveals a clinical significance. Journal of human genetics 38 30498240
2015 Cav1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine Release in Chromaffin Cells. Current molecular pharmacology 38 25966692
2012 Retrocochlear function of the peripheral deafness gene Cacna1d. Human molecular genetics 38 22678062
1991 A brain L-type calcium channel alpha 1 subunit gene (CCHL1A2) maps to mouse chromosome 14 and human chromosome 3. Genomics 38 1664412
2015 Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice. Scientific reports 37 26381090
2014 CaV1.3 L-type channels, maxiK Ca(2+)-dependent K(+) channels and bestrophin-1 regulate rhythmic photoreceptor outer segment phagocytosis by retinal pigment epithelial cells. Cellular signalling 35 24407175
2010 Expression and roles of Cav1.3 (α1D) L-type Ca²+ channel in atrioventricular node automaticity. Journal of molecular and cellular cardiology 35 20951705
2017 Ca2+ protein alpha 1D of CaV1.3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity. Scientific reports 34 29079724
2008 CaV1.2 rather than CaV1.3 is coupled to glucose-stimulated insulin secretion in INS-1 832/13 cells. Journal of molecular endocrinology 33 18562674
2020 A de novo CACNA1D missense mutation in a patient with congenital hyperinsulinism, primary hyperaldosteronism and hypotonia. Channels (Austin, Tex.) 32 32336187
2016 Regulation of aldosterone secretion by Cav1.3. Scientific reports 32 27098837
2012 Equal sensitivity of Cav1.2 and Cav1.3 channels to the opposing modulations of PKA and PKG in mouse chromaffin cells. The Journal of physiology 32 22826131
2014 C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca(2+) channels. Biophysical journal 31 24703308
2013 Harmonin enhances voltage-dependent facilitation of Cav1.3 channels and synchronous exocytosis in mouse inner hair cells. The Journal of physiology 31 23613530
2012 Cav1.3 and Cav1.2 channels of adrenal chromaffin cells: emerging views on cAMP/cGMP-mediated phosphorylation and role in pacemaking. Biochimica et biophysica acta 31 23159773
2016 An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation. Scientific reports 30 27255217
2008 Expression of calcium channel CaV1.3 in cat spinal cord: light and electron microscopic immunohistochemical study. The Journal of comparative neurology 30 18095323
2019 Genetic silencing of striatal CaV1.3 prevents and ameliorates levodopa dyskinesia. Movement disorders : official journal of the Movement Disorder Society 27 31002755
2009 Cav1.2 and Cav1.3 are differentially coupled to glucagon-like peptide-1 potentiation of glucose-stimulated insulin secretion in the pancreatic beta-cell line INS-1. The Journal of pharmacology and experimental therapeutics 27 19710366
2015 LRP1B, BRD2 and CACNA1D: new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia. Epigenomics 25 26586120
2012 Structural determinants of CaV1.3 L-type calcium channel gating. Channels (Austin, Tex.) 25 22760075
2009 The intracellular II-III loops of Cav1.2 and Cav1.3 uncouple L-type voltage-gated Ca2+ channels from glucagon-like peptide-1 potentiation of insulin secretion in INS-1 cells via displacement from lipid rafts. The Journal of pharmacology and experimental therapeutics 25 19351867
2018 Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9. Nucleic acids research 24 29733375
2006 Protein kinase C activation inhibits Cav1.3 calcium channel at NH2-terminal serine 81 phosphorylation site. American journal of physiology. Heart and circulatory physiology 24 16973824
2006 Differential modulation of Cav1.2 and Cav1.3-mediated glucose-stimulated insulin secretion by cAMP in INS-1 cells: distinct roles for exchange protein directly activated by cAMP 2 (Epac2) and protein kinase A. The Journal of pharmacology and experimental therapeutics 23 16565168
2018 [The third case report a patient with primary aldosteronism, seizures, and neurologic abnormalities (PASNA) syndrome de novo variant mutations in the CACNA1D gene]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 22 30698561
2010 Direct interaction and functional coupling between voltage-gated CaV1.3 Ca2+ channel and GABAB receptor subunit 2. FEBS letters 22 20627102
2005 Subtype switching of L-Type Ca 2+ channel from Cav1.3 to Cav1.2 in embryonic murine ventricle. Circulation journal : official journal of the Japanese Circulation Society 22 16247219
2020 Channelopathies of voltage-gated L-type Cav1.3/α1D and T-type Cav3.1/α1G Ca2+ channels in dysfunction of heart automaticity. Pflugers Archiv : European journal of physiology 21 32601767
2009 Enhancement of calcium transport in Caco-2 monolayer through PKCzeta-dependent Cav1.3-mediated transcellular and rectifying paracellular pathways by prolactin. American journal of physiology. Cell physiology 21 19339512
2016 Rescuing cardiac automaticity in L-type Cav1.3 channelopathies and beyond. The Journal of physiology 20 27374078
2017 Reduction of Cav1.3 channels in dorsal hippocampus impairs the development of dentate gyrus newborn neurons and hippocampal-dependent memory tasks. PloS one 19 28715454
2016 A Rare Variant in CACNA1D Segregates with 7 Bipolar I Disorder Cases in a Large Pedigree. Molecular neuropsychiatry 19 27867939
2011 Perinatal and postnatal expression of Cav1.3 α1D Ca²⁺ channel in the rat heart. Pediatric research 19 21378599
2004 Cav1.3 is preferentially coupled to glucose-induced [Ca2+]i oscillations in the pancreatic beta cell line INS-1. Molecular pharmacology 19 15102955

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