Gene Symbol: CACNA1I
Description: calcium voltage-gated channel subunit alpha1 I
Alias: Cav3.3, ca(v)3.3, voltage-dependent T-type calcium channel subunit alpha-1I, calcium channel, voltage-dependent, T type, alpha 1I subunit, calcium channel, voltage-dependent, alpha 1I subunit, voltage-gated calcium channel subunit alpha Cav3.3
Species: human
Products:     CACNA1I

Top Publications

  1. Jurkovicova Tarabova B, Cmarko L, Rehak R, Zamponi G, Lacinova L, Weiss N. Identification of a molecular gating determinant within the carboxy terminal region of Cav3.3 T-type channels. Mol Brain. 2019;12:34 pubmed publisher
    ..Altogether, our data are consistent with a model in which the carboxy terminus stabilizes the channel in a closed state. ..
  2. Sanchez Roige S, Fontanillas P, Elson S, Gray J, de Wit H, MacKillop J, et al. Genome-Wide Association Studies of Impulsive Personality Traits (BIS-11 and UPPS-P) and Drug Experimentation in up to 22,861 Adult Research Participants Identify Loci in the CACNA1I and CADM2 genes. J Neurosci. 2019;39:2562-2572 pubmed publisher
    ..68 with rs139528938). Furthermore, genetic variants in the CACNA1I locus were significantly associated with UPPS-P Negative Urgency (p = 3...
  3. Cheng X, Ma L, Feng X, Zhu M, Zhang D, Xu L, et al. Antigen retrieval pre-treatment causes a different expression pattern of Cav3.2 in rat and mouse spinal dorsal horn. Eur J Histochem. 2019;63: pubmed publisher
    ..2 but not GFAP. Together, our findings indicate that AR pre-treatment or not impacts the expression pattern of Cav3.2, which may make a significant contribution to the future study of Cav3.2 in SDH. ..
  4. Lee B, Koeppel A, Wang E, Gonzalez T, Sun T, Kroener L, et al. Differential gene expression during placentation in pregnancies conceived with different fertility treatments compared with spontaneous pregnancies. Fertil Steril. 2019;111:535-546 pubmed publisher
    ..There was one protein-coding differentially expressed gene (DEG) between the spontaneous and infertility groups, CACNA1I, one protein-coding DEG between the spontaneous and IVF groups, CACNA1I, and five protein-coding DEGs between the ..
  5. Elíes J, Johnson E, Boyle J, Scragg J, Peers C. H2S does not regulate proliferation via T-type Ca2+ channels. Biochem Biophys Res Commun. 2015;461:659-64 pubmed publisher
    ..1. Our data indicate that inhibition of T-type Ca(2+) channel-mediated proliferation by H2S is independent of the channels' sensitivity to H2S. ..
  6. Staehlke S, Koertge A, Nebe B. Intracellular calcium dynamics dependent on defined microtopographical features of titanium. Biomaterials. 2015;46:48-57 pubmed publisher
    ..The topography-dependent calcium dynamics observed here provide new insights into how topographical cues alter cell functions - via the intracellular Ca(2+) signaling. ..
  7. Monteil A, Chausson P, Boutourlinsky K, Mezghrani A, Huc Brandt S, Blesneac I, et al. Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop. J Biol Chem. 2015;290:16168-76 pubmed publisher
    ..2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels. ..
  8. Fekete A, Johnston J, Delaney K. Presynaptic T-type Ca2+ channels modulate dendrodendritic mitral-mitral and mitral-periglomerular connections in mouse olfactory bulb. J Neurosci. 2014;34:14032-45 pubmed publisher
    ..Deinactivation of Cav3.x channels by hyperpolarization increases T-type Ca(2+) influx upon repolarization and increases feedback inhibition to produce subthreshold modulation of the mitral-periglomerular reciprocal circuit. ..
  9. Elíes J, Scragg J, Huang S, Dallas M, Huang D, MacDougall D, et al. Hydrogen sulfide inhibits Cav3.2 T-type Ca2+ channels. FASEB J. 2014;28:5376-87 pubmed publisher
    ..Our data demonstrate a novel target for H2S regulation, the T-type Ca(2+) channel Cav3.2, and suggest that such modulation cannot account for the pronociceptive effects of this gasotransmitter. ..

More Information


  1. Tomášová L, Pavlovicová M, Malekova L, Misak A, Kristek F, Grman M, et al. Effects of AP39, a novel triphenylphosphonium derivatised anethole dithiolethione hydrogen sulfide donor, on rat haemodynamic parameters and chloride and calcium Cav3 and RyR2 channels. Nitric Oxide. 2015;46:131-44 pubmed publisher
  2. Kumar D, Dedic N, Flachskamm C, Voulé S, Deussing J, Kimura M. Cacna1c (Cav1.2) Modulates Electroencephalographic Rhythm and Rapid Eye Movement Sleep Recovery. Sleep. 2015;38:1371-80 pubmed publisher
    ..Lower spectral gamma activity, slightly increased sleep demands, and altered REM sleep responses found in heterozygous Cacna1c knockout mice may rather resemble a sleep phenotype observed in schizophrenia patients. ..
  3. Tompkins J, Merriam L, Girard B, May V, Parsons R. Nickel suppresses the PACAP-induced increase in guinea pig cardiac neuron excitability. Am J Physiol Cell Physiol. 2015;308:C857-66 pubmed publisher
    ..Together, our results suggest that a PACAP-enhanced, Ni(2+)-sensitive current contributes to PACAP-induced modulation of neuronal excitability. ..
  4. Harraz O, Visser F, Brett S, Goldman D, Zechariah A, Hashad A, et al. CaV1.2/CaV3.x channels mediate divergent vasomotor responses in human cerebral arteries. J Gen Physiol. 2015;145:405-18 pubmed publisher
    ..In conclusion, this study documents the expression of three distinct Ca(2+) channel subtypes in human cerebral arteries and further shows how they act together to orchestrate arterial tone. ..
  5. Kim M, Jung H, Kim S, Park J, Seo Y. Electromagnetic fields and nanomagnetic particles increase the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Int J Mol Med. 2015;35:153-60 pubmed publisher
    ..Furthermore, the mRNA expression of calcium channels (CACNA1C, CACNA1E, CACNA1G and CACNA1I) was activated during osteogenic differentiation...
  6. Banciu A, Banciu D, Mustaciosu C, Radu M, Cretoiu D, Xiao J, et al. Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium. Int J Mol Sci. 2018;19: pubmed publisher
  7. Calderón Rivera A, Sandoval A, González Ramírez R, González Billault C, Felix R. Regulation of neuronal cav3.1 channels by cyclin-dependent kinase 5 (Cdk5). PLoS ONE. 2015;10:e0119134 pubmed publisher
    ..1subunit. These results highlight a novel role for Cdk5 in the regulation of T-type Ca2+ channels. ..
  8. Watanabe M, Ueda T, Shibata Y, Kumamoto N, Shimada S, Ugawa S. Expression and Regulation of Cav3.2 T-Type Calcium Channels during Inflammatory Hyperalgesia in Mouse Dorsal Root Ganglion Neurons. PLoS ONE. 2015;10:e0127572 pubmed publisher
  9. Wen X, Li X, Li H, Liang H, Yang C, Wang H. CaMK II γ down regulation protects dorsal root ganglion neurons from ropivacaine hydrochloride neurotoxicity. Sci Rep. 2017;7:5262 pubmed publisher
    ..2 and Cav3.3 expression. In conclusion, CaMKIIγ regulated Cav3.2 and Cav3.3 expression in DRG, which was involved with ropivacaine hydrochloride-induced cell injury. ..
  10. Gadotti V, Bladen C, Zhang F, Chen L, Gündüz M, Şimşek R, et al. Analgesic effect of a broad-spectrum dihydropyridine inhibitor of voltage-gated calcium channels. Pflugers Arch. 2015;467:2485-93 pubmed publisher
    ..3 (T-type) and Cav2.2 (N-type) currents. Altogether, our data indicate that broad-spectrum inhibition of multiple calcium channel subtypes can lead to potent analgesia in rodents. ..
  11. Pudukulatham Z, Zhang F, Gadotti V, M Dahoma S, Swami P, Tamboli Y, et al. Synthesis and characterization of a disubstituted piperazine derivative with T-type channel blocking action and analgesic properties. Mol Pain. 2016;12: pubmed publisher
    ..2 channels. Altogether, our data identify a novel T-type calcium channel blocker with tight structure activity relationship (SAR) and relevant in vivo efficacy in inflammatory pain conditions. ..
  12. Andrade A, Hope J, Allen A, Yorgan V, Lipscombe D, Pan J. A rare schizophrenia risk variant of CACNA1I disrupts CaV3.3 channel activity. Sci Rep. 2016;6:34233 pubmed publisher
    b>CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human CaV3.3 ?1 subunit, a subtype of voltage-gated calcium channel that contributes to T-type currents...
  13. Yabuki Y, Matsuo K, Izumi H, Haga H, Yoshida T, Wakamori M, et al. Pharmacological properties of SAK3, a novel T-type voltage-gated Ca2+ channel enhancer. Neuropharmacology. 2017;117:1-13 pubmed publisher
    ..1 knockout (KO) mice. These findings suggest overall that T-VGCCs play a key role in cognition by enhancing hippocampal ACh release and that the cognitive enhancer SAK3 could be a candidate therapeutic in Alzheimer's disease. ..
  14. Yang W, Li Q, Wang S, Gao F, Qian W, Li F, et al. Cannabinoid receptor agonists modulate calcium channels in rat retinal Müller cells. Neuroscience. 2016;313:213-24 pubmed publisher
    ..The existence of receptor-dependent and -independent mechanisms suggests that cannabinoids may modulate Müller cell functions through multiple pathways. ..
  15. Cain S, Ahn S, Garcia E, Zhang Y, Waheed Z, Tyson J, et al. Heantos-4, a natural plant extract used in the treatment of drug addiction, modulates T-type calcium channels and thalamocortical burst-firing. Mol Brain. 2016;9:94 pubmed
  16. Weaver E, Zamora F, Hearne J, Martin Caraballo M. Posttranscriptional regulation of T-type Ca(2+) channel expression by interleukin-6 in prostate cancer cells. Cytokine. 2015;76:309-320 pubmed publisher
    ..These results indicate that the functional expression of T-type Ca(2+) channels is regulated by the interplay of multiple factors in LNCaP cells. ..
  17. Sharop B, Boldyriev O, Batiuk M, Shtefan N, Shuba Y. Compensatory reduction of Cav3.1 expression in thalamocortical neurons of juvenile rats of WAG/Rij model of absence epilepsy. Epilepsy Res. 2016;119:10-2 pubmed publisher
    ..The weakened expression of Cav3.1 in juveniles of WAG/Rij rats could represent a compensatory mechanism determining the pattern of the age dependency in the disease manifestation by this model of absence epilepsy. ..
  18. Liu D, Lu J, Zhao Q, Hu C, Mei Y. Growth differentiation factor-15 promotes glutamate release in medial prefrontal cortex of mice through upregulation of T-type calcium channels. Sci Rep. 2016;6:28653 pubmed publisher
  19. Manoach D, Pan J, PURCELL S, Stickgold R. Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?. Biol Psychiatry. 2016;80:599-608 pubmed publisher
    ..For example, the SZ risk gene CACNA1I encodes a calcium channel that is abundantly expressed in the thalamic spindle generator and plays a critical ..
  20. Jeong K, Lee S, Seo H, Oh Y, Jang D, Choe J, et al. Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep. Sci Rep. 2015;5:17893 pubmed publisher
    ..Thus, our study suggests invertebrate T-type Ca(2+) channels promote wakefulness rather than stabilizing sleep. ..
  21. Karmažínová M, JaÅ¡ková K, Griac P, Perez Reyes E, Lacinová Ä. Contrasting the roles of the I-II loop gating brake in CaV3.1 and CaV3.3 calcium channels. Pflugers Arch. 2015;467:2519-27 pubmed publisher
    ..We suggest that activation of the voltage sensor in domain I is limiting both the voltage dependence and the kinetics of CaV3 channel activation. ..
  22. Zhang D, Chen J, Saraf A, Cassar S, Han P, Rogers J, et al. Association of Catsper1 or -2 with Ca(v)3.3 leads to suppression of T-type calcium channel activity. J Biol Chem. 2006;281:22332-41 pubmed
    ..These studies demonstrate that CatSper1 and CatSper2 can associate with and modulate the function of the Ca(v)3.3 channel, which might be important in the regulation of sperm function. ..
  23. Smith C, Abdallah S, Wong Y, Le P, Harracksingh A, Artinian L, et al. Evolutionary insights into T-type Ca2+ channel structure, function, and ion selectivity from the Trichoplax adhaerens homologue. J Gen Physiol. 2017;149:483-510 pubmed publisher
    ..TCav3 is the most divergent metazoan T-type calcium channel and thus provides an evolutionary perspective on Cav3 channel structure-function properties, ion selectivity, and cellular physiology. ..
  24. Shan H, Hammarback J, Godwin D. Ethanol inhibition of a T-type Ca²+ channel through activity of protein kinase C. Alcohol Clin Exp Res. 2013;37:1333-42 pubmed publisher
    ..EtOH primarily affects the CaV3.2 isoform of T-type Ca²? channels acting through PKC, highlighting a novel target and mechanism for EtOH effects on excitable membranes. ..
  25. Xu W, Liu Y, Chen J, Guo Q, Liu K, Wen Z, et al. Genetic risk between the CACNA1I gene and schizophrenia in Chinese Uygur population. Hereditas. 2018;155:5 pubmed publisher
    ..Recent researches indicated that the CACNA1I involved in calcium channels probably affect the potential pathogenesis of SCZ...
  26. Fornaro L, Vivaldi C, Lin D, Xue H, Falcone A, Wang Y, et al. Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation. PLoS ONE. 2017;12:e0182818 pubmed publisher
    ..Alterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation. ..
  27. Chemin J, Taiakina V, Monteil A, Piazza M, Guan W, Stephens R, et al. Calmodulin regulates Cav3 T-type channels at their gating brake. J Biol Chem. 2017;292:20010-20031 pubmed publisher
    ..Our findings may have implications for arrhythmia disorders arising from mutations in the gating brake or CaM. ..
  28. Xie Y, Huang D, Wei L, Luo X. Further evidence for the genetic association between CACNA1I and schizophrenia. Hereditas. 2018;155:16 pubmed publisher
    ..between genetic variants in three calcium signaling pathway genes (CACNB2, CACNA1C and CACNA1I) and SCZ in 1615 SCZ cases and 1597 controls...
  29. Catterall W, Perez Reyes E, Snutch T, Striessnig J. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev. 2005;57:411-25 pubmed
    ..This article presents the molecular relationships and physiological functions of these calcium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties. ..
  30. Murbartián J, Arias J, Perez Reyes E. Functional impact of alternative splicing of human T-type Cav3.3 calcium channels. J Neurophysiol. 2004;92:3399-407 pubmed
    ..The CACNA1I gene encodes the Cav3.3 isoform, which activates and inactivates much more slowly than the other Cav3 channels...
  31. Hildebrand M, David L, Hamid J, Mulatz K, Garcia E, Zamponi G, et al. Selective inhibition of Cav3.3 T-type calcium channels by Galphaq/11-coupled muscarinic acetylcholine receptors. J Biol Chem. 2007;282:21043-55 pubmed
    ..3 channel are necessary and sufficient for complete M1 receptor-mediated channel inhibition and represent novel sites not previously implicated in T-type channel modulation. ..
  32. Mittman S, Guo J, Emerick M, Agnew W. Structure and alternative splicing of the gene encoding alpha1I, a human brain T calcium channel alpha1 subunit. Neurosci Lett. 1999;269:121-4 pubmed
    The structure of CACNA1I, the gene encoding alpha1I, a human brain T Ca2+ channel alpha1 subunit, was determined by comparison of polymerase chain reaction-amplified brain cDNA and genomic sequences...
  33. Lee N, Jeong S, Kim K, Kim J, Park J, Kang H, et al. Ca2+ Regulation of Cav3.3 T-type Ca2+ Channel Is Mediated by Calmodulin. Mol Pharmacol. 2017;92:347-357 pubmed publisher
    ..3. Taken together, our results suggest that Cav3.3 T-type channel is potently regulated by Ca2+i via interaction of Ca2+/CaM with the carboxyl terminus of Cav3.3. ..
  34. Wang J, Zhang Y, Liang J, Pan H, Wu H, Xu K, et al. CACNA1I is not associated with childhood absence epilepsy in the Chinese Han population. Pediatr Neurol. 2006;35:187-90 pubmed
    This study investigated whether the T-type calcium channel gene CACNA1I causes susceptibility in the Chinese Han population to childhood absence epilepsy, a form of idiopathic generalized seizure disorder...
  35. Wen X, Liang H, Li H, Ou W, Wang H, Liu H, et al. In vitro neurotoxicity by ropivacaine is reduced by silencing Cav3.3 T-type calcium subunits in neonatal rat sensory neurons. Artif Cells Nanomed Biotechnol. 2017;:1-8 pubmed publisher
    ..Cav3.3 can regulate CaMKII? mRNA and protein expression. In conclusion, Cav3.3 regulated CaMKII? in DRG, which was involved with the cell injury induced by ropivacaine hydrochloride...
  36. Sun H, Varela D, Chartier D, Ruben P, Nattel S, Zamponi G, et al. Differential interactions of Na+ channel toxins with T-type Ca2+ channels. J Gen Physiol. 2008;132:101-13 pubmed publisher
  37. . Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia. Biol Psychiatry. 2012;72:620-8 pubmed publisher
    ..This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci. ..
  38. Basson M, Zeng B, Downey C, Sirivelu M, Tepe J. Increased extracellular pressure stimulates tumor proliferation by a mechanosensitive calcium channel and PKC-β. Mol Oncol. 2015;9:513-26 pubmed publisher
    ..Targeting this pathway may inhibit proliferation in large unresectable tumors. ..
  39. Gomora J, Murbartián J, Arias J, Lee J, Perez Reyes E. Cloning and expression of the human T-type channel Ca(v)3.3: insights into prepulse facilitation. Biophys J. 2002;83:229-41 pubmed
    ..Therefore, Ca(v)3.3 is similar to high voltage-activated Ca(2+) channels in that depolarizing prepulses can regulate their activity, and their carboxy termini play a role in modulating channel activity. ..
  40. Chemin J, Monteil A, Perez Reyes E, Bourinet E, Nargeot J, Lory P. Specific contribution of human T-type calcium channel isotypes (alpha(1G), alpha(1H) and alpha(1I)) to neuronal excitability. J Physiol. 2002;540:3-14 pubmed
  41. Glauser T, Holland K, O Brien V, Keddache M, Martin L, Clark P, et al. Pharmacogenetics of antiepileptic drug efficacy in childhood absence epilepsy. Ann Neurol. 2017;81:444-453 pubmed publisher
    To determine whether common polymorphisms in CACNA1G, CACNA1H, CACNA1I, and ABCB1 are associated with differential short-term seizure outcome in childhood absence epilepsy (CAE)...
  42. Weiss N, Lacinova L. T-type channels: release a brake, engage a gear. Channels (Austin). 2016;10:78-80 pubmed publisher
  43. Monteil A, Chemin J, Leuranguer V, Altier C, Mennessier G, Bourinet E, et al. Specific properties of T-type calcium channels generated by the human alpha 1I subunit. J Biol Chem. 2000;275:16530-5 pubmed