t type calcium channels


Summary: A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.

Top Publications

  1. Obejero Paz C, Gray I, Jones S. Y3+ block demonstrates an intracellular activation gate for the alpha1G T-type Ca2+ channel. J Gen Physiol. 2004;124:631-40 pubmed
    ..Since an extracellular blocker can rapidly enter the closed pore, the primary activation gate must be on the intracellular side of the selectivity filter. ..
  2. 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. ..
  3. Pathirathna S, Brimelow B, Jagodic M, Krishnan K, Jiang X, Zorumski C, et al. New evidence that both T-type calcium channels and GABAA channels are responsible for the potent peripheral analgesic effects of 5alpha-reduced neuroactive steroids. Pain. 2005;114:429-43 pubmed
    ..Our results also reveal a role of GABA-gated ion channels in peripheral nociceptive signaling. ..
  4. Park J, Kang H, Moon H, Huh S, Jeong S, Soldatov N, et al. Activation of protein kinase C augments T-type Ca2+ channel activity without changing channel surface density. J Physiol. 2006;577:513-23 pubmed
    ..1 T-type channels was not significantly changed by activation of PKC. The PKC effect on Cav3.1 was localized to the cytoplasmic II-III loop using chimeric channels with individual cytoplasmic loops of Cav3.1 replaced by those of Cav2.1. ..
  5. Kang H, Park J, Jeong S, Kim J, Moon H, Perez Reyes E, et al. A molecular determinant of nickel inhibition in Cav3.2 T-type calcium channels. J Biol Chem. 2006;281:4823-30 pubmed
    ..1. These findings indicate that His-191 in the S3-S4 loop is a critical residue conferring nickel block to Ca(v)3.2 and reveal a novel role for the S3-S4 loop to control ion permeation through T-type Ca2+ channels. ..
  6. Zhong X, Liu J, Kyle J, Hanck D, Agnew W. A profile of alternative RNA splicing and transcript variation of CACNA1H, a human T-channel gene candidate for idiopathic generalized epilepsies. Hum Mol Genet. 2006;15:1497-512 pubmed
    ..We discuss a paradigm for CACNA1H expression of Ca(v)3.2 subunits, which may influence future basic and clinical studies. ..
  7. Emerick M, Stein R, Kunze R, McNulty M, Regan M, Hanck D, et al. Profiling the array of Ca(v)3.1 variants from the human T-type calcium channel gene CACNA1G: alternative structures, developmental expression, and biophysical variations. Proteins. 2006;64:320-42 pubmed
    ..We conclude that the structural gene and networks of splicing regulatory factors define an integrated system for the phenotypic variation of Ca(v)3.1 biophysics during nervous system development. ..
  8. Perez Reyes E. Molecular characterization of T-type calcium channels. Cell Calcium. 2006;40:89-96 pubmed
    ..This section reviews the structure of T-channels, how splicing affects structure and function, how SNPs alter channel activity, and how high voltage-activated auxiliary subunits affect T-channels. ..
  9. McNulty M, Kyle J, Lipkind G, Hanck D. An inner pore residue (Asn406) in the Nav1.5 channel controls slow inactivation and enhances mibefradil block to T-type Ca2+ channel levels. Mol Pharmacol. 2006;70:1514-23 pubmed
    ..Channels did not slow-inactivate, however, at the voltages used to assay mibefradil block, supporting the idea that Asn406 lies within or near the mibefradil binding site. ..

More Information


  1. Choi S, Na H, Kim J, Lee J, Lee S, Kim D, et al. Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels. Genes Brain Behav. 2007;6:425-31 pubmed
    ..The present study reveals that the Ca(V)3.2 subtype of T-type Ca(2+) channels are important in the peripheral processing of noxious signals, regardless of modality, duration or affected tissue type...
  2. Talavera K, Nilius B. Evidence for common structural determinants of activation and inactivation in T-type Ca2+ channels. Pflugers Arch. 2006;453:189-201 pubmed
    ..1. Our results indicate that common structures, most likely the S6 transmembrane segments, are involved in the conformational changes occurring during both channel activation and inactivation. ..
  3. Jagodic M, Pathirathna S, Nelson M, Mancuso S, Joksovic P, Rosenberg E, et al. Cell-specific alterations of T-type calcium current in painful diabetic neuropathy enhance excitability of sensory neurons. J Neurosci. 2007;27:3305-16 pubmed
  4. Shcheglovitov A, Kostyuk P, Shuba Y. Selectivity signatures of three isoforms of recombinant T-type Ca2+ channels. Biochim Biophys Acta. 2007;1768:1406-19 pubmed
    ..1 and Ca(v)3.3, is likely to possess an extracellular Ca(2+) binding site that controls channel permeation. Our results provide novel functional tests for identifying subunits responsible for T-type Ca(2+) current in native cells. ..
  5. 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. ..
  6. Khan N, Gray I, Obejero Paz C, Jones S. Permeation and gating in CaV3.1 (alpha1G) T-type calcium channels effects of Ca2+, Ba2+, Mg2+, and Na+. J Gen Physiol. 2008;132:223-38 pubmed publisher
    ..Voltage strongly affects the concentration dependence of block, but not of permeation, for Ca(2+) or Ba(2+)...
  7. Obejero Paz C, Gray I, Jones S. Ni2+ block of CaV3.1 (alpha1G) T-type calcium channels. J Gen Physiol. 2008;132:239-50 pubmed publisher
    ..1, inhibition of Ca(V)3.2 by Ni(2+) was essentially independent of voltage, and was similar in 2 mM Ca(2+) vs. Ba(2+), consistent with inhibition by a different mechanism, at a site outside the pore...
  8. 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. ..
  9. Ernst W, Zhang Y, Yoo J, Ernst S, Noebels J. Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence epilepsy. J Neurosci. 2009;29:1615-25 pubmed publisher
  10. Vassort G, Talavera K, Alvarez J. Role of T-type Ca2+ channels in the heart. Cell Calcium. 2006;40:205-20 pubmed
    ..ICaT contributes also to Ca2+-dependent hormonal secretion. This review further emphasizes the difficulties encountered in analysing this current. ..
  11. Lacinova L. Voltage-dependent calcium channels. Gen Physiol Biophys. 2005;24 Suppl 1:1-78 pubmed
    ..Transfer of 30 % of charge correlates with activation of 70 % of measurable macroscopic current. Prolonged depolarization does not immobilize charge movement of the Ca(v)3.1 channel. ..
  12. Arias J, Murbartián J, Vitko I, Lee J, Perez Reyes E. Transfer of beta subunit regulation from high to low voltage-gated Ca2+ channels. FEBS Lett. 2005;579:3907-12 pubmed
    ..Taken together, these results support a direct coupling model where beta subunits alter movements in IS6 that occur as the channel transits between closed, open, and inactivated states. ..
  13. Nelson M, Joksovic P, Perez Reyes E, Todorovic S. The endogenous redox agent L-cysteine induces T-type Ca2+ channel-dependent sensitization of a novel subpopulation of rat peripheral nociceptors. J Neurosci. 2005;25:8766-75 pubmed
  14. Moosmang S, Haider N, Brüderl B, Welling A, Hofmann F. Antihypertensive effects of the putative T-type calcium channel antagonist mibefradil are mediated by the L-type calcium channel Cav1.2. Circ Res. 2006;98:105-10 pubmed
    ..2SMAKO mice. These results demonstrate that the effect of the putative T-type Ca2+ channel-selective blocker mibefradil on blood pressure and small vessel myogenic tone is mediated by the Cav1.2 L-type Ca2+ channel. ..
  15. Nelson M, Woo J, Kang H, Vitko I, Barrett P, Perez Reyes E, et al. Reducing agents sensitize C-type nociceptors by relieving high-affinity zinc inhibition of T-type calcium channels. J Neurosci. 2007;27:8250-60 pubmed
    ..2 and nociceptor excitability. ..
  16. Jensen L, Holstein Rathlou N. Is there a role for T-type Ca2+ channels in regulation of vasomotor tone in mesenteric arterioles?. Can J Physiol Pharmacol. 2009;87:8-20 pubmed publisher
    ..The first direct demonstration of endothelial T-type channels warrants new investigations of their role in vascular biology. ..
  17. Talavera K, Janssens A, Klugbauer N, Droogmans G, Nilius B. Extracellular Ca2+ modulates the effects of protons on gating and conduction properties of the T-type Ca2+ channel alpha1G (CaV3.1). J Gen Physiol. 2003;121:511-28 pubmed
  18. Chemin J, Nargeot J, Lory P. Neuronal T-type alpha 1H calcium channels induce neuritogenesis and expression of high-voltage-activated calcium channels in the NG108-15 cell line. J Neurosci. 2002;22:6856-62 pubmed
  19. Chemin J, Monteil A, Perez Reyes E, Nargeot J, Lory P. Direct inhibition of T-type calcium channels by the endogenous cannabinoid anandamide. EMBO J. 2001;20:7033-40 pubmed
    ..Our data demonstrate that anandamide inhibition of T-channels can regulate neuronal excitability and account for CB receptor-independent effects of this signaling molecule. ..
  20. Talavera K, Staes M, Janssens A, Klugbauer N, Droogmans G, Hofmann F, et al. Aspartate residues of the Glu-Glu-Asp-Asp (EEDD) pore locus control selectivity and permeation of the T-type Ca(2+) channel alpha(1G). J Biol Chem. 2001;276:45628-35 pubmed
    ..The mutation of both divergent aspartates only partially confers HVA channel permeation properties to the alpha(1G) Ca(2+) channel subunit. ..
  21. Kaku T, Lee T, Arita M, Hadama T, Ono K. The gating and conductance properties of Cav3.2 low-voltage-activated T-type calcium channels. Jpn J Physiol. 2003;53:165-72 pubmed
    ..The properties relating to progression and recovery from inactivation in the Ca(V)3.2 channel are substantially identical with either Ca(2+) or Ba(2+) as the charge carrier. ..
  22. Swensen A, Bean B. Ionic mechanisms of burst firing in dissociated Purkinje neurons. J Neurosci. 2003;23:9650-63 pubmed
  23. Todorovic S, Jevtovic Todorovic V, Meyenburg A, Mennerick S, Perez Reyes E, Romano C, et al. Redox modulation of T-type calcium channels in rat peripheral nociceptors. Neuron. 2001;31:75-85 pubmed
    ..These data strongly suggest a role for T channels in peripheral nociception. Redox sites on T channels in peripheral nociceptors could be important targets for agents that modify pain perception. ..
  24. Dubel S, Altier C, Chaumont S, Lory P, Bourinet E, Nargeot J. Plasma membrane expression of T-type calcium channel alpha(1) subunits is modulated by high voltage-activated auxiliary subunits. J Biol Chem. 2004;279:29263-9 pubmed
  25. Song I, Kim D, Choi S, Sun M, Kim Y, Shin H. Role of the alpha1G T-type calcium channel in spontaneous absence seizures in mutant mice. J Neurosci. 2004;24:5249-57 pubmed
  26. Lacinova L, Klugbauer N, Hofmann F. Gating of the expressed Cav3.1 calcium channel. FEBS Lett. 2002;531:235-40 pubmed
    ..9 mV and +12.3 mV and with slopes of 22.4 mV and 18.1 mV for the ON- and OFF-charge movement, respectively. Inactivation of I(Ca) by prolonged depolarization pulse did not immobilize intramembrane charge movement in the Cav3.1 channel. ..
  27. Gustafsson F, Andreasen D, Salomonsson M, Jensen B, Holstein Rathlou N. Conducted vasoconstriction in rat mesenteric arterioles: role for dihydropyridine-insensitive Ca(2+) channels. Am J Physiol Heart Circ Physiol. 2001;280:H582-90 pubmed
    ..Rather, the vasoconstrictor responses appear to rely on other types of voltage-gated, dihydropyridine-insensitive Ca(2+) channels, possibly of the T-type. ..
  28. Chemin J, Monteil A, Bourinet E, Nargeot J, Lory P. Alternatively spliced alpha(1G) (Ca(V)3.1) intracellular loops promote specific T-type Ca(2+) channel gating properties. Biophys J. 2001;80:1238-50 pubmed
    ..Altogether, these data demonstrate that expression of distinct variants for the T-type alpha(1G) subunit can account for specific low-voltage-activated currents observed in neuronal tissues. ..
  29. Fareh S, Benardeau A, Nattel S. Differential efficacy of L- and T-type calcium channel blockers in preventing tachycardia-induced atrial remodeling in dogs. Cardiovasc Res. 2001;49:762-70 pubmed
    ..These findings are potentially important for understanding the mechanisms and prevention of clinically-relevant atrial-tachycardia-induced remodeling. ..
  30. Kuo C, Yang S. Recovery from inactivation of t-type ca2+ channels in rat thalamic neurons. J Neurosci. 2001;21:1884-92 pubmed
    ..T-channels thus might have a more rigid hinge and a more abrupt conformational change in the inactivation machinery associated with opening and closing of the pore. ..
  31. Burgess D, Crawford O, Delisle B, Satin J. Mechanism of inactivation gating of human T-type (low-voltage activated) calcium channels. Biophys J. 2002;82:1894-906 pubmed
    ..We have integrated these concepts into an eight-state kinetic model, which can account for the major characteristics of T-type Ca channel inactivation. ..
  32. Todorovic S, Meyenburg A, Jevtovic Todorovic V. Mechanical and thermal antinociception in rats following systemic administration of mibefradil, a T-type calcium channel blocker. Brain Res. 2002;951:336-40 pubmed
    ..This suggests that peripherally acting T-type Ca(2+) channel blockers can be useful antinociceptive agents. ..
  33. Vanbavel E, Sorop O, Andreasen D, Pfaffendorf M, Jensen B. Role of T-type calcium channels in myogenic tone of skeletal muscle resistance arteries. Am J Physiol Heart Circ Physiol. 2002;283:H2239-43 pubmed
    ..6 +/- 0.1 (n = 5); K(+) -5.4 +/- 0.3 (n = 4); all log(IC(50)) P < 0.05, basal vs. K(+)]. These data suggest that T-type calcium channels are expressed and involved in maintenance of myogenic tone in rat cremaster muscle arterioles. ..
  34. Ikeda H, Heinke B, Ruscheweyh R, Sandkühler J. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science. 2003;299:1237-40 pubmed
    ..Thereby, memory traces of painful events are retained. ..
  35. Yunker A, Sharp A, Sundarraj S, Ranganathan V, Copeland T, McEnery M. Immunological characterization of T-type voltage-dependent calcium channel CaV3.1 (alpha 1G) and CaV3.3 (alpha 1I) isoforms reveal differences in their localization, expression, and neural development. Neuroscience. 2003;117:321-35 pubmed
    ..Taken together, these data provide an anatomical and biochemical basis for interpreting LVA heterogeneity and offer evidence of developmental regulation of LVA isoform expression. ..
  36. Park J, Jeong S, Perez Reyes E, Lee J. Modulation of Ca(v)3.2 T-type Ca2+ channels by protein kinase C. FEBS Lett. 2003;547:37-42 pubmed
    ..Our findings suggest that PMA upregulates Ca(v)3.2 channel activity via activation of oocyte PKC. ..
  37. Jeong S, Park B, Park J, Lee J, Lee J. Divalent metals differentially block cloned T-type calcium channels. Neuroreport. 2003;14:1537-40 pubmed
    ..Conversely, Pb2+ block on Ca2+ channels did not show distinctive selectivity. Taken together, these results suggest that besides Ni2+, Cu2+ and Zn2+ can be used as selective blockers of alpha1 H at low concentrations. ..
  38. Todorovic S, Meyenburg A, Jevtovic Todorovic V. Redox modulation of peripheral T-type Ca2+ channels in vivo: alteration of nerve injury-induced thermal hyperalgesia. Pain. 2004;109:328-39 pubmed
    ..Since thermal hyperalgesia is a common symptom of axonal injury, locally applied oxidizing agents could be used as a novel treatment to ameliorate neuropathic pain. ..
  39. Huang L, Keyser B, Tagmose T, Hansen J, Taylor J, Zhuang H, et al. NNC 55-0396 [(1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride]: a new selective inhibitor of T-type calcium channels. J Pharmacol Exp Ther. 2004;309:193-9 pubmed
    ..We conclude that NNC 55-0396, by virtue of its modified structure, does not produce the metabolite that causes inhibition of L-type Ca2+ channels, thus rendering it more selective to T-type Ca2+ channels. ..
  40. Staes M, Talavera K, Klugbauer N, Prenen J, Lacinova L, Droogmans G, et al. The amino side of the C-terminus determines fast inactivation of the T-type calcium channel alpha1G. J Physiol. 2001;530:35-45 pubmed
  41. Talavera K, Janssens A, Klugbauer N, Droogmans G, Nilius B. Pore structure influences gating properties of the T-type Ca2+ channel alpha1G. J Gen Physiol. 2003;121:529-40 pubmed
    ..These changes are independent of the alterations of the selectivity properties and channel protonation. ..
  42. Frazier C, Serrano J, George E, Yu X, Viswanathan A, Perez Reyes E, et al. Gating kinetics of the alpha1I T-type calcium channel. J Gen Physiol. 2001;118:457-70 pubmed
    ..This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability. ..
  43. 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
    ..3 channels provides a mechanism for fine-tuning the latency and duration of low-threshold spikes. ..
  44. Dubreuil A, Boukhaddaoui H, Desmadryl G, Martinez Salgado C, Moshourab R, Lewin G, et al. Role of T-type calcium current in identified D-hair mechanoreceptor neurons studied in vitro. J Neurosci. 2004;24:8480-4 pubmed
    ..Indeed, the properties of the T-type amplifier are particularly well suited to explain the high sensitivity of D-hair mechanoreceptors to slowly moving stimuli. ..
  45. Cribbs L, Martin B, Schroder E, Keller B, Delisle B, Satin J. Identification of the t-type calcium channel (Ca(v)3.1d) in developing mouse heart. Circ Res. 2001;88:403-7 pubmed
    ..We demonstrate that 100 micromol/L Ni(2+) partially blocked alpha1G currents under physiological external Ca(2+). We conclude that alpha1G T-type Ca(2+) channels are functional in midgestational fetal myocardium. ..
  46. Heady T, Gomora J, Macdonald T, Perez Reyes E. Molecular pharmacology of T-type Ca2+ channels. Jpn J Pharmacol. 2001;85:339-50 pubmed
  47. Kim D, Song I, Keum S, Lee T, Jeong M, Kim S, et al. Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2+) channels. Neuron. 2001;31:35-45 pubmed
    ..Thus, the modulation of the intrinsic firing pattern mediated by alpha(1G) T-type Ca(2+) channels plays a critical role in the genesis of absence seizures in the thalamocortical pathway. ..
  48. Hansen P, Jensen B, Andreasen D, Skøtt O. Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels. Circ Res. 2001;89:630-8 pubmed
  49. Marksteiner R, Schurr P, Berjukow S, Margreiter E, Perez Reyes E, Hering S. Inactivation determinants in segment IIIS6 of Ca(v)3.1. J Physiol. 2001;537:27-34 pubmed
    ..1 (Hering et al. 1998) have a significant role in Ca(v)3.1 inactivation. These data suggest common elements in the molecular architecture of the inactivation mechanism in high and low threshold Ca(2+) channels. ..
  50. Dogrul A, Gardell L, Ossipov M, Tulunay F, Lai J, Porreca F. Reversal of experimental neuropathic pain by T-type calcium channel blockers. Pain. 2003;105:159-68 pubmed
    ..The data support the view that selective T-type calcium channel blockers may have significant potential in the treatment of neuropathic pain states. ..
  51. Zhang Y, Vilaythong A, Yoshor D, Noebels J. Elevated thalamic low-voltage-activated currents precede the onset of absence epilepsy in the SNAP25-deficient mouse mutant coloboma. J Neurosci. 2004;24:5239-48 pubmed
    ..We suggest that presynaptic release defects shared by these mutants lead to postsynaptic LVA excitability increases in thalamic pacemaker neurons that favor rebound bursting and absence epilepsy. ..
  52. Perez Reyes E. Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev. 2003;83:117-61 pubmed
    ..The Cav3 subtypes can be differentiated by their kinetics and sensitivity to block by Ni2+. The goal of this review is to provide a comprehensive description of T-type currents, their distribution, regulation, pharmacology, and cloning. ..
  53. Shin J, Martinez Salgado C, Heppenstall P, Lewin G. A T-type calcium channel required for normal function of a mammalian mechanoreceptor. Nat Neurosci. 2003;6:724-30 pubmed
    ..This is the first evidence that a calcium channel is required for normal function of a vertebrate mechanoreceptor. ..