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The Journal of Neuroscience, March 15, 1999, 19(6):1895-1911

Differential Distribution of Three Members of a Gene Family Encoding Low Voltage-Activated (T-Type) Calcium Channels

Edmund M. Talley¹, Leanne L. Cribbs², Jung-Ha Lee², Asif Daud², Edward Perez-Reyes², and Douglas A. Bayliss¹

¹ Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, and ² Department of Physiology, Loyola University Medical Center, Maywood, Illinois 60153

Low voltage-activated (T-type) calcium currents are observed in many central and peripheral neurons and display distinct physiological and functional properties. Using in situ hybridization, we have localized central and peripheral nervous system expression of three transcripts (1G, 1H, and 1I) of the T-type calcium channel family (Ca_VT). Each mRNA demonstrated a unique distribution, and expression of the three genes was largely complementary. We found high levels of expression of these transcripts in regions associated with prominent T-type currents, including inferior olivary and thalamic relay neurons (which expressed 1G), sensory ganglia, pituitary, and dentate gyrus granule neurons (1H), and thalamic reticular neurons (1I and 1H). Other regions of high expression included the Purkinje cell layer of the cerebellum, the bed nucleus of the stria terminalis, the claustrum (1G), the olfactory tubercles (1H and 1I), and the subthalamic nucleus (1I and 1G). Some neurons expressed high levels of all three genes, including hippocampal pyramidal neurons and olfactory granule cells. Many brain regions showed a predominance of labeling for 1G, including the amygdala, cerebral cortex, rostral hypothalamus, brainstem, and spinal cord. Exceptions included the basal ganglia, which showed more prominent labeling for 1H and 1I, and the olfactory bulb, the hippocampus, and the caudal hypothalamus, which showed more even levels of all three transcripts. Our results are consistent with the hypothesis that differential gene expression underlies pharmacological and physiological heterogeneity observed in neuronal T-type calcium currents, and they provide a molecular basis for the study of T-type channels in particular neurons.

Key words: in situ hybridization; calcium channel; CNS; anticonvulsant; rat; T-type calcium channels

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Copyright © 1999 Society for Neuroscience  0270-6474/99/1961895-17$05.00/0

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				M. Russier, E. Carlier, N. Ankri, L. Fronzaroli, and D. Debanne A-, T-, and H-type Currents Shape Intrinsic Firing of Developing Rat Abducens Motoneurons J. Physiol., May 15, 2003; 549(1): 21 - 36. [Abstract] [Full Text] [PDF]

				R. K. Cloues and W. A. Sather Afterhyperpolarization Regulates Firing Rate in Neurons of the Suprachiasmatic Nucleus J. Neurosci., March 1, 2003; 23(5): 1593 - 1604. [Abstract] [Full Text] [PDF]

				D. M. Porcello, S. D. Smith, and J. R. Huguenard Actions of U-92032, a T-Type Ca2+ Channel Antagonist, Support a Functional Linkage Between IT and Slow Intrathalamic Rhythms J Neurophysiol, January 1, 2003; 89(1): 177 - 185. [Abstract] [Full Text] [PDF]

				E. Perez-Reyes Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels Physiol Rev, January 1, 2003; 83(1): 117 - 161. [Abstract] [Full Text] [PDF]

				J. Chemin, J. Nargeot, and P. Lory 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., August 15, 2002; 22(16): 6856 - 6862. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				J. Wolfart and J. Roeper Selective Coupling of T-Type Calcium Channels to SK Potassium Channels Prevents Intrinsic Bursting in Dopaminergic Midbrain Neurons J. Neurosci., May 1, 2002; 22(9): 3404 - 3413. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				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]

				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]

				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]

				S.-N. YANG, J. YU, G. W. MAYR, F. HOFMANN, O. LARSSON, and P.-O. BERGGREN Inositol hexakisphosphate increases L-type Ca2+ channel activity by stimulation of adenylyl cyclase FASEB J, August 1, 2001; 15(10): 1753 - 1763. [Abstract] [Full Text] [PDF]

				M. Ito Cerebellar Long-Term Depression: Characterization, Signal Transduction, and Functional Roles Physiol Rev, July 1, 2001; 81(3): 1143 - 1195. [Abstract] [Full Text] [PDF]

				P J Green, R Warre, P D Hayes, N C L McNaughton, A D Medhurst, M Pangalos, D M Duckworth, and A D Randall Kinetic modification of the {alpha}1I subunit-mediated T-type Ca2+ channel by a human neuronal Ca2+ channel {gamma} subunit J. Physiol., June 1, 2001; 533(2): 467 - 478. [Abstract] [Full Text] [PDF]

				S. Brevi, M. de Curtis, and J. Magistretti Pharmacological and Biophysical Characterization of Voltage-Gated Calcium Currents in the Endopiriform Nucleus of the Guinea Pig J Neurophysiol, May 1, 2001; 85(5): 2076 - 2087. [Abstract] [Full Text] [PDF]

				Q.-Q. Sun, J. R Huguenard, and D. A Prince Neuropeptide Y receptors differentially modulate G-protein-activated inwardly rectifying K+ channels and high-voltage-activated Ca2+ channels in rat thalamic neurons J. Physiol., February 15, 2001; 531(1): 67 - 79. [Abstract] [Full Text] [PDF]

				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]

				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]

				W.-J. Song, Y. Baba, T. Otsuka, and F. Murakami Characterization of Ca2+ Channels in Rat Subthalamic Nucleus Neurons J Neurophysiol, November 1, 2000; 84(5): 2630 - 2637. [Abstract] [Full Text] [PDF]

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