Cacna1h

Summary

Gene Symbol: Cacna1h
Description: calcium voltage-gated channel subunit alpha1 H
Alias: voltage-dependent T-type calcium channel subunit alpha-1H, calcium channel, voltage-dependent, T type, alpha 1H subunit, voltage-gated calcium channel subunit alpha Cav3.2
Species: rat
Products:     Cacna1h

Top Publications

  1. Jacus M, Uebele V, Renger J, Todorovic S. Presynaptic Cav3.2 channels regulate excitatory neurotransmission in nociceptive dorsal horn neurons. J Neurosci. 2012;32:9374-82 pubmed publisher
    ..These studies provide previously unknown information regarding the role of presynaptic T-channels in nociceptive signaling in the spinal cord. ..
  2. Marger F, Gelot A, Alloui A, Matricon J, Ferrer J, Barrere C, et al. T-type calcium channels contribute to colonic hypersensitivity in a rat model of irritable bowel syndrome. Proc Natl Acad Sci U S A. 2011;108:11268-73 pubmed publisher
    ..2 as a promising target for the development of efficient analgesics for the visceral discomfort and pain associated with IBS. ..
  3. Kang H, Vitko I, Lee S, Perez Reyes E, Lee J. Structural determinants of the high affinity extracellular zinc binding site on Cav3.2 T-type calcium channels. J Biol Chem. 2010;285:3271-81 pubmed publisher
    ..These studies provide insight into the structure of T-type channels, and identify an extracellular motif that could be targeted for drug development. ..
  4. Gouriou Y, Bijlenga P, Demaurex N. Mitochondrial Ca2+ uptake from plasma membrane Cav3.2 protein channels contributes to ischemic toxicity in PC12 cells. J Biol Chem. 2013;288:12459-68 pubmed publisher
    ..1/Cav3.2 silencing. We conclude that the opening of Cav3.2 channels during ischemia contribute to the entry of Ca(2+) ions that are transmitted to mitochondria, resulting in a deleterious mitochondrial Ca(2+) overload. ..
  5. Rzhepetskyy Y, Lazniewska J, Proft J, Campiglio M, Flucher B, Weiss N. A Cav3.2/Stac1 molecular complex controls T-type channel expression at the plasma membrane. Channels (Austin). 2016;10:346-354 pubmed
    ..Altogether, our data establish Stac1 as an important modulator of T-type channel expression and provide new insights into the molecular mechanisms underlying the trafficking of T-type channels to the plasma membrane. ..
  6. Markandeya Y, Fahey J, Pluteanu F, Cribbs L, Balijepalli R. Caveolin-3 regulates protein kinase A modulation of the Ca(V)3.2 (alpha1H) T-type Ca2+ channels. J Biol Chem. 2011;286:2433-44 pubmed publisher
    ..Our findings on functional modulation of the Ca(v)3.2 channels by Cav-3 is important for understanding the compartmentalized regulation of Ca(2+) signaling during normal and pathological processes. ..
  7. Orestes P, Bojadzic D, Lee J, Leach E, Salajegheh R, Digruccio M, et al. Free radical signalling underlies inhibition of CaV3.2 T-type calcium channels by nitrous oxide in the pain pathway. J Physiol. 2011;589:135-48 pubmed publisher
    ..These findings reveal a novel mechanism of interaction between N2O and ion channels, furthering our understanding of this widely used analgesic in pain processing...
  8. Somekawa S, Imagawa K, Naya N, Takemoto Y, Onoue K, Okayama S, et al. Regulation of aldosterone and cortisol production by the transcriptional repressor neuron restrictive silencer factor. Endocrinology. 2009;150:3110-7 pubmed publisher
    ..We found a NRSE-like sequence in human CYP11B2 and CYP11B1 genes as well as the CACNA1H gene of many mammalian species. The CACNA1H gene encodes the alpha-subunit of Cav3.2...
  9. Bourinet E, Alloui A, Monteil A, Barrere C, Couette B, Poirot O, et al. Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO J. 2005;24:315-24 pubmed
    ..Taken together, the results provide direct evidence linking CaV3.2 T-type channels to pain perception and suggest that CaV3.2 may offer a specific molecular target for the treatment of pain. ..

More Information

Publications41

  1. Sellak H, Zhou C, Liu B, Chen H, Lincoln T, Wu S. Transcriptional regulation of ?1H T-type calcium channel under hypoxia. Am J Physiol Cell Physiol. 2014;307:C648-56 pubmed publisher
    ..Taken together, these findings indicate that hypoxia-induced ?1H upregulation involves binding of hypoxia-inducible factor to an HRE within the ?1H promoter region. ..
  2. Carabelli V, Marcantoni A, Comunanza V, De Luca A, Diaz J, Borges R, et al. Chronic hypoxia up-regulates alpha1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells. J Physiol. 2007;584:149-65 pubmed
  3. Catterall W. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011;3:a003947 pubmed publisher
    ..This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties. ..
  4. McRory J, Santi C, Hamming K, Mezeyova J, Sutton K, Baillie D, et al. Molecular and functional characterization of a family of rat brain T-type calcium channels. J Biol Chem. 2001;276:3999-4011 pubmed
  5. Rose K, Lunardi N, Boscolo A, Dong X, Erisir A, Jevtovic Todorovic V, et al. Immunohistological demonstration of CaV3.2 T-type voltage-gated calcium channel expression in soma of dorsal root ganglion neurons and peripheral axons of rat and mouse. Neuroscience. 2013;250:263-74 pubmed publisher
    ..The CaV3.2 expression within the soma and peripheral axons of nociceptive sensory neurons further demonstrates the importance of this channel in peripheral pain transmission. ..
  6. Lee J, Nelson M, Rose K, Todorovic S. Redox mechanism of S-nitrosothiol modulation of neuronal CaV3.2 T-type calcium channels. Mol Neurobiol. 2013;48:274-80 pubmed publisher
  7. Witkovsky P, Shen C, McRory J. Differential distribution of voltage-gated calcium channels in dopaminergic neurons of the rat retina. J Comp Neurol. 2006;497:384-96 pubmed
    ..Our findings are consistent with the available pharmacological data indicating that alpha1A and alpha1B calcium channels control the major fraction of dopamine release in the rat retina. ..
  8. Powell K, Tang H, Ng C, Guillemain I, Dieuset G, Dezsi G, et al. Seizure expression, behavior, and brain morphology differences in colonies of Genetic Absence Epilepsy Rats from Strasbourg. Epilepsia. 2014;55:1959-68 pubmed publisher
    ..A previously identified mutation in the Cacna1h gene controlling the CaV 3...
  9. Braunstein T, Inoue R, Cribbs L, Oike M, Ito Y, Holstein Rathlou N, et al. The role of L- and T-type calcium channels in local and remote calcium responses in rat mesenteric terminal arterioles. J Vasc Res. 2009;46:138-51 pubmed publisher
    ..Both L- and T-type channels mediate Ca(2+) entry during conducted vasoconstriction to local KCl in mesenteric arterioles. However, these channels do not participate in the conduction process per se. ..
  10. 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. ..
  11. Pluteanu F, Cribbs L. T-type calcium channels are regulated by hypoxia/reoxygenation in ventricular myocytes. Am J Physiol Heart Circ Physiol. 2009;297:H1304-13 pubmed publisher
    ..Our results demonstrate that Ca(v)3.1 and Ca(v)3.2 T-type calcium channels are differentially regulated by hypoxia/reoxygenation injury, and, therefore, they may serve different functions in the myocyte in response to hypoxic injury. ..
  12. Chen Y, Lu J, Pan H, Zhang Y, Wu H, Xu K, et al. Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol. 2003;54:239-43 pubmed
    Direct sequencing of exons 3 to 35 and the exon-intron boundaries of the CACNA1H gene was conducted in 118 childhood absence epilepsy patients of Han ethnicity recruited from North China...
  13. Joksovic P, Nelson M, Jevtovic Todorovic V, Patel M, Perez Reyes E, Campbell K, et al. CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus. J Physiol. 2006;574:415-30 pubmed
  14. Maturana A, Lenglet S, Python M, Kuroda S, Rossier M. Role of the T-type calcium channel CaV3.2 in the chronotropic action of corticosteroids in isolated rat ventricular myocytes. Endocrinology. 2009;150:3726-34 pubmed publisher
    ..These results provide a molecular model that could explain the high incidence of arrhythmias observed in patients upon combination of inappropriate activation of the mineralocorticoid receptor and oxidative stress. ..
  15. Van Loo K, Schaub C, Pernhorst K, Yaari Y, Beck H, Schoch S, et al. Transcriptional regulation of T-type calcium channel CaV3.2: bi-directionality by early growth response 1 (Egr1) and repressor element 1 (RE-1) protein-silencing transcription factor (REST). J Biol Chem. 2012;287:15489-501 pubmed publisher
    ..2 (Cacna1h). First, we determined the promoter region and observed several stimulatory and inhibitory clusters...
  16. Takahashi T, Aoki Y, Okubo K, Maeda Y, Sekiguchi F, Mitani K, et al. Upregulation of Ca(v)3.2 T-type calcium channels targeted by endogenous hydrogen sulfide contributes to maintenance of neuropathic pain. Pain. 2010;150:183-91 pubmed publisher
    ..We thus propose that Ca(v)3.2 and CSE could be targets for the development of therapeutic drugs for the treatment of neuropathic pain. ..
  17. Khosravani H, Altier C, Simms B, Hamming K, Snutch T, Mezeyova J, et al. Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy. J Biol Chem. 2004;279:9681-4 pubmed
    ..Chan, P., Shen, Y., and Wu, X. (2003) Ann. Neurol. 54, 239-243) 12 missense mutations were identified in the CACNA1H (Ca(v)3.2) gene in 14 of 118 patients with CAE but not in 230 control individuals...
  18. Okubo K, Takahashi T, Sekiguchi F, Kanaoka D, Matsunami M, Ohkubo T, et al. Inhibition of T-type calcium channels and hydrogen sulfide-forming enzyme reverses paclitaxel-evoked neuropathic hyperalgesia in rats. Neuroscience. 2011;188:148-56 pubmed publisher
    ..2 and CSE at protein levels, differing from the previous evidence for the neuropathic pain model induced by spinal nerve cutting in which Ca(v)3.2 was dramatically upregulated in DRG. ..
  19. Marni F, Wang Y, Morishima M, Shimaoka T, Uchino T, Zheng M, et al. 17 beta-estradiol modulates expression of low-voltage-activated Ca(V)3.2 T-type calcium channel via extracellularly regulated kinase pathway in cardiomyocytes. Endocrinology. 2009;150:879-88 pubmed publisher
    ..2 I(Ca,T) through activation of ERK-1/2, 5, which is mediated by the suppression of Csx/Nkx2.5-dependent transcription, suggesting a genomic effect of E(2) as a negative chronotropic factor in the heart. ..
  20. Khomula E, Viatchenko Karpinski V, Borisyuk A, Duzhyy D, Belan P, Voitenko N. Specific functioning of Cav3.2 T-type calcium and TRPV1 channels under different types of STZ-diabetic neuropathy. Biochim Biophys Acta. 2013;1832:636-49 pubmed publisher
    ..These findings indicate that alterations in functioning of Cav3.2 T-type and TRPV1 channels, specific for each type of PDN, may underlie the variety of pain syndromes induced by type 1 diabetes. ..
  21. Li Y, Tatsui C, Rhines L, North R, Harrison D, Cassidy R, et al. Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated T-type calcium channels (Cav3.2) in paclitaxel-induced peripheral neuropathy. Pain. 2017;158:417-429 pubmed publisher
    ..Furthermore, ML218 hydrochloride decreased firing frequency in human DRG, where spontaneous action potentials were present. In summary, Cav3.2 in concert with TLR4 in DRG neurons appears to contribute to paclitaxel-induced neuropathy. ..
  22. José O, Hernandez Hernandez O, Chirinos M, González González M, Larrea F, Almanza A, et al. Recombinant human ZP3-induced sperm acrosome reaction: evidence for the involvement of T- and L-type voltage-gated calcium channels. Biochem Biophys Res Commun. 2010;395:530-4 pubmed publisher
    ..Consistent with this, we detected in human sperm transcripts for the Ca(V)1 auxiliary subunits, alpha(2)delta, beta(1), beta(2) and beta(4), but not the neuronal specific isoforms beta(3) and gamma(2). ..
  23. Lee W, Orestes P, Latham J, Naik A, Nelson M, Vitko I, et al. Molecular mechanisms of lipoic acid modulation of T-type calcium channels in pain pathway. J Neurosci. 2009;29:9500-9 pubmed publisher
    ..This study provides the first mechanistic demonstration of a nociceptive ion channel modulation that may contribute to the documented analgesic properties of lipoic acid in vivo. ..
  24. Maeda Y, Aoki Y, Sekiguchi F, Matsunami M, Takahashi T, Nishikawa H, et al. Hyperalgesia induced by spinal and peripheral hydrogen sulfide: evidence for involvement of Cav3.2 T-type calcium channels. Pain. 2009;142:127-32 pubmed publisher
    ..2 T-type Ca2+ channels expressed in the primary afferents and/or spinal nociceptive neurons, leading to sensitization of nociceptive processing and hyperalgesia. ..
  25. Iftinca M, McKay B, Snutch T, McRory J, Turner R, Zamponi G. Temperature dependence of T-type calcium channel gating. Neuroscience. 2006;142:1031-42 pubmed
    ..3, but not rat Ca(v)3.3. The observed changes in the kinetics were significant but not identical for the three isoforms, showing that the ability of T-type channels to conduct calcium varies with both channel isoform and temperature. ..
  26. Molineux M, McRory J, McKay B, Hamid J, Mehaffey W, Rehak R, et al. Specific T-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons. Proc Natl Acad Sci U S A. 2006;103:5555-60 pubmed
    ..The Ca(v)3 class of LVA calcium channels is thus expressed in specific combinations in a wide range of cerebellar neurons but contributes to rebound burst discharge in only a select number of cell classes. ..
  27. Yue J, Liu L, Liu Z, Shu B, Zhang Y. Upregulation of T-type Ca2+ channels in primary sensory neurons in spinal nerve injury. Spine (Phila Pa 1976). 2013;38:463-70 pubmed publisher
  28. Huang C, Chen Y, Chen C. Physical interaction between calcineurin and Cav3.2 T-type Ca2+ channel modulates their functions. FEBS Lett. 2013;587:1723-30 pubmed publisher
    ..2 regulates calcineurin/NFAT pathway through both the Ca(2+) influx and calcineurin binding. Our findings unveiled a reciprocal regulation of Ca(2+) signaling which contributes to our understanding of cardiac hypertrophy. ..
  29. Navarro Gonzalez M, Grayson T, Meaney K, Cribbs L, Hill C. Non-L-type voltage-dependent calcium channels control vascular tone of the rat basilar artery. Clin Exp Pharmacol Physiol. 2009;36:55-66 pubmed publisher
    ..1, which may impact on channel activity. 8. We conclude that vascular tone of the rat basilar artery results from calcium influx through nifedipine-insensitive VDCCs with pharmacology consistent with Ca(V)3.1 T-type channels. ..
  30. González Rodríguez P, Falcón D, Castro M, Ureña J, López Barneo J, Castellano A. Hypoxic induction of T-type Ca(2+) channels in rat cardiac myocytes: role of HIF-1α and RhoA/ROCK signalling. J Physiol. 2015;593:4729-45 pubmed publisher
    ..These results suggest a possible role for Cav 3.2 channels in the increased probability of developing arrhythmias observed in ischaemic situations, and in the pathogenesis of diseases associated with hypoxic Ca(2+) overload. ..
  31. Lenglet S, Louiset E, Delarue C, Vaudry H, Contesse V. Involvement of T-type calcium channels in the mechanism of action of 5-HT in rat glomerulosa cells: a novel signaling pathway for the 5-HT7 receptor. Endocr Res. 2002;28:651-5 pubmed
    ..Both the activation of the AC/PKA pathway and the calcium influx are involved in 5-HT-induced aldosterone secretion. ..
  32. Abd El Rahman R, Harraz O, Brett S, Anfinogenova Y, Mufti R, Goldman D, et al. Identification of L- and T-type Ca2+ channels in rat cerebral arteries: role in myogenic tone development. Am J Physiol Heart Circ Physiol. 2013;304:H58-71 pubmed publisher
    ..Both conductances contribute to myogenic tone, although their overall contribution is unequal...