© 1998 American Heart Association, Inc.
Rapid Communications |
Cloning and Characterization of 
1H From Human Heart, a Member of the T-Type Ca2+ Channel Gene Family
From the Department of Physiology (L.L.C., J.-H.L., J.Y., A.D., E.P.-R.) and the Cardiovascular Institute (L.L.C., E.P.-R.), Loyola University Medical Center, Maywood, Ill; the Department of Physiology (J.S., Y.Z.), University of Kentucky, Lexington, Ky; the Department of Paediatrics (J.B., M.P.W., M.R.), The Rayne Institute, University College London Medical School, London, UK; and the MRC Human Biochemical Genetics Unit (M.F.), The Galton Laboratory, London, UK.
Correspondence to Leanne L. Cribbs, Department of Physiology, Loyola University Medical Center, 2160 South First Ave, Maywood, IL 60153. E-mail lcribbs{at}luc.edu
Abstract—Voltage-activated
Ca2+ channels exist as multigene families that share common
structural features. Different Ca2+ channels are
distinguished by their electrophysiology and pharmacology and can be
classified as either low or high voltage–activated channels.
Six 1 subunit genes cloned previously code for high
voltage–activated Ca2+ channels; therefore, we
have used a database search strategy to identify new Ca2+
channel genes, possibly including low voltage–activated
(T-type) channels. A novel expressed sequence–tagged cDNA clone of
1G was used to screen a cDNA library, and in the present
study, we report the cloning of 1H (or CavT.2), a low
voltage–activated Ca2+ channel from human heart.
Northern blots of human mRNA detected more 1H expression in
peripheral tissues, such as kidney and heart, than in
brain. We mapped the gene, CACNA1H, to human chromosome
16p13.3 and mouse chromosome 17. Expression of 1H in HEK-293 cells
resulted in Ca2+ channel currents displaying voltage
dependence, kinetics, and unitary conductance characteristic of native
T-type Ca2+ channels. The 1H channel is sensitive to
mibefradil, a nondihydropyridine Ca2+
channel blocker, with an IC50 of 1.4 µmol/L,
consistent with the reported potency of mibefradil for T-type
Ca2+ channels. Together with 1G, a rat brain T-type
Ca2+ channel also cloned in our laboratory, these genes
define a unique family of Ca2+ channels.
Key Words: T-type Ca2+ channel • 1 subunit • cloning • mibefradil
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Y. Zhang, M. Mori, D. L. Burgess, and J. L. Noebels Mutations in High-Voltage-Activated Calcium Channel Genes Stimulate Low-Voltage-Activated Currents in Mouse Thalamic Relay Neurons J. Neurosci., August 1, 2002; 22(15): 6362 - 6371. [Abstract] [Full Text] [PDF]
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D. Sochivko, A. Pereverzev, N. Smyth, C. Gissel, T. Schneider, and H. Beck The CaV2.3 Ca2+ channel subunit contributes to R-Type Ca2+ currents in murine hippocampal and neocortical neurones J. Physiol., August 1, 2002; 542(3): 699 - 710. [Abstract] [Full Text] [PDF]
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K. Hirooka, G. E. Bertolesi, M. E. M. Kelly, E. M. Denovan-Wright, X. Sun, J. Hamid, G. W. Zamponi, A. E. Juhasz, L. W. Haynes, and S. Barnes T-Type Calcium Channel alpha 1G and alpha 1H Subunits in Human Retinoblastoma Cells and Their Loss After Differentiation J Neurophysiol, July 1, 2002; 88(1): 196 - 205. [Abstract] [Full Text] [PDF]
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J.-H. Lee, E.-G. Kim, B.-G. Park, K.-H. Kim, S.-K. Cha, I. D. Kong, J.-W. Lee, and S.-W. Jeong Identification of T-Type alpha 1H Ca2+ Channels (Cav3.2) in Major Pelvic Ganglion Neurons J Neurophysiol, June 1, 2002; 87(6): 2844 - 2850. [Abstract] [Full Text] [PDF]
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H. Su, D. Sochivko, A. Becker, J. Chen, Y. Jiang, Y. Yaari, and H. Beck Upregulation of a T-Type Ca2+ Channel Causes a Long-Lasting Modification of Neuronal Firing Mode after Status Epilepticus J. Neurosci., May 1, 2002; 22(9): 3645 - 3655. [Abstract] [Full Text] [PDF]
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J. Chemin, A. Monteil, E. Perez-Reyes, E. Bourinet, J. Nargeot, and P. Lory Specific contribution of human T-type calcium channel isotypes ({alpha}1G, {alpha}1H and {alpha}1I) to neuronal excitability J. Physiol., April 1, 2002; 540(1): 3 - 14. [Abstract] [Full Text] [PDF]
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P. Mariot, K. Vanoverberghe, N. Lalevee, M. F. Rossier, and N. Prevarskaya Overexpression of an alpha 1H (Cav3.2) T-type Calcium Channel during Neuroendocrine Differentiation of Human Prostate Cancer Cells J. Biol. Chem., March 22, 2002; 277(13): 10824 - 10833. [Abstract] [Full Text] [PDF]
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C. Berthier, A. Monteil, P. Lory, and C. Strube {alpha}1H mRNA in single skeletal muscle fibres accounts for T-type calcium current transient expression during fetal development in mice J. Physiol., March 15, 2002; 539(3): 681 - 691. [Abstract] [Full Text] [PDF]
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G. Michels, J. Matthes, R. Handrock, U. Kuchinke, F. Groner, L. L. Cribbs, A. Pereverzev, T. Schneider, E. Perez-Reyes, and S. Herzig Single-Channel Pharmacology of Mibefradil in Human Native T-Type and Recombinant Cav3.2 Calcium Channels Mol. Pharmacol., March 1, 2002; 61(3): 682 - 694. [Abstract] [Full Text] [PDF]
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S. Jagannathan, E. L. Punt, Y. Gu, C. Arnoult, D. Sakkas, C. L. R. Barratt, and S. J. Publicover Identification and Localization of T-type Voltage-operated Calcium Channel Subunits in Human Male Germ Cells. EXPRESSION OF MULTIPLE ISOFORMS J. Biol. Chem., March 1, 2002; 277(10): 8449 - 8456. [Abstract] [Full Text] [PDF]
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C. M. Santi, F. S. Cayabyab, K. G. Sutton, J. E. McRory, J. Mezeyova, K. S. Hamming, D. Parker, A. Stea, and T. P. Snutch Differential Inhibition of T-Type Calcium Channels by Neuroleptics J. Neurosci., January 15, 2002; 22(2): 396 - 403. [Abstract] [Full Text] [PDF]
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J. T Wolfe, H. Wang, E. Perez-Reyes, and P. Q Barrett Stimulation of recombinant Cav3.2, T-type, Ca2+ channel currents by CaMKII{gamma}C J. Physiol., January 15, 2002; 538(2): 343 - 355. [Abstract] [Full Text] [PDF]
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K. Talavera, M. Staes, A. Janssens, N. Klugbauer, G. Droogmans, F. Hofmann, and B. Nilius Aspartate Residues of the Glu-Glu-Asp-Asp (EEDD) Pore Locus Control Selectivity and Permeation of the T-type Ca2+ Channel alpha 1G J. Biol. Chem., November 30, 2001; 276(49): 45628 - 45635. [Abstract] [Full Text] [PDF]
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C. J. Frazier, J. R. Serrano, E. G. George, X. Yu, A. Viswanathan, E. Perez-Reyes, and S. W. Jones Gating Kinetics of the {alpha}1i T-Type Calcium Channel J. Gen. Physiol., November 1, 2001; 118(5): 457 - 470. [Abstract] [Full Text] [PDF]
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J. C. Gomora, A. N. Daud, M. Weiergraber, and E. Perez-Reyes Block of Cloned Human T-Type Calcium Channels by Succinimide Antiepileptic Drugs Mol. Pharmacol., November 1, 2001; 60(5): 1121 - 1132. [Abstract] [Full Text] [PDF]
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O. Lesouhaitier, A. Chiappe, and M. F. Rossier Aldosterone Increases T-Type Calcium Currents in Human Adrenocarcinoma (H295R) Cells by Inducing Channel Expression Endocrinology, October 1, 2001; 142(10): 4320 - 4330. [Abstract] [Full Text] [PDF]
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L. L. Cribbs Vascular Smooth Muscle Calcium Channels: Could "T" Be a Target? Circ. Res., September 28, 2001; 89(7): 560 - 562. [Full Text] [PDF]
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S. M. Todorovic, V. Jevtovic-Todorovic, S. Mennerick, E. Perez-Reyes, and C. F. Zorumski Cav3.2 Channel Is a Molecular Substrate for Inhibition of T-Type Calcium Currents in Rat Sensory Neurons by Nitrous Oxide Mol. Pharmacol., September 1, 2001; 60(3): 603 - 610. [Abstract] [Full Text] [PDF]
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 S. L. Lipsius, J. Huser, and L. A. Blatter Intracellular Ca2+ Release Sparks Atrial Pacemaker Activity Physiology, June 1, 2001; 16(3): 101 - 106. [Abstract] [Full Text] [PDF]
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 K. A. Griffin, M. Picken, G. L. Bakris, and A. K. Bidani Comparative Effects of Selective T- and L-Type Calcium Channel Blockers in the Remnant Kidney Model Hypertension, May 1, 2001; 37(5): 1268 - 1272. [Abstract] [Full Text] [PDF]
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 G.-Q. Xiao, K. Hu, and M. Boutjdir Direct Inhibition of Expressed Cardiac L- and T-Type Calcium Channels by IgG From Mothers Whose Children Have Congenital Heart Block Circulation, March 20, 2001; 103(11): 1599 - 1604. [Abstract] [Full Text] [PDF]
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L. L. Cribbs, B. L. Martin, E. A. Schroder, B. B. Keller, B. P. Delisle, and J. Satin Identification of the T-Type Calcium Channel (CaV3.1d) in Developing Mouse Heart Circ. Res., March 2, 2001; 88(4): 403 - 407. [Abstract] [Full Text] [PDF]
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A. D. Schrier, H. Wang, E. M. Talley, E. Perez-Reyes, and P. Q. Barrett {alpha}1H T-type Ca2+ channel is the predominant subtype expressed in bovine and rat zona glomerulosa Am J Physiol Cell Physiol, February 1, 2001; 280(2): C265 - C272. [Abstract] [Full Text] [PDF]
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M. Staes, K. Talavera, N. Klugbauer, J. Prenen, L. Lacinova, G. Droogmans, F. Hofmann, and B. Nilius The amino side of the C-terminus determines fast inactivation of the T-type calcium channel {alpha}1G J. Physiol., January 1, 2001; 530(1): 35 - 45. [Abstract] [Full Text] [PDF]
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M. Tateyama, S. Zong, T. Tanabe, and R. Ochi Properties of voltage-gated Ca2+ channels in rabbit ventricular myocytes expressing Ca2+ channel {alpha}1E cDNA Am J Physiol Cell Physiol, January 1, 2001; 280(1): C175 - C182. [Abstract] [Full Text] [PDF]
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S. M. Wilson, P. T. Toth, S. B. Oh, S. E. Gillard, S. Volsen, D. Ren, L. H. Philipson, E. C. Lee, C. F. Fletcher, L. Tessarollo, et al. The Status of Voltage-Dependent Calcium Channels in alpha 1E Knock-Out Mice J. Neurosci., December 1, 2000; 20(23): 8566 - 8571. [Abstract] [Full Text] [PDF]
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P. Q. Barrett, H.-K. Lu, R. Colbran, A. Czernik, and J. J. Pancrazio Stimulation of unitary T-type Ca2+ channel currents by calmodulin-dependent protein kinase II Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1694 - C1703. [Abstract] [Full Text] [PDF]
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Y. Takagishi, K. Yasui, N. J. Severs, and Y. Murata Species-specific difference in distribution of voltage-gated L-type Ca2+ channels of cardiac myocytes Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1963 - C1969. [Abstract] [Full Text] [PDF]
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R. C. Foehring, P. G. Mermelstein, W.-J. Song, S. Ulrich, and D. J. Surmeier Unique Properties of R-Type Calcium Currents in Neocortical and Neostriatal Neurons J Neurophysiol, November 1, 2000; 84(5): 2225 - 2236. [Abstract] [Full Text] [PDF]
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V. Leuranguer, A. Monteil, E. Bourinet, G. Dayanithi, and J. Nargeot T-type calcium currents in rat cardiomyocytes during postnatal development: contribution to hormone secretion Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2540 - H2548. [Abstract] [Full Text] [PDF]
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