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The Journal of Neuroscience, March 15, 1999, 19(6):1912-1921
Cloning and Expression of a Novel Member of the Low
Voltage-Activated T-Type Calcium Channel Family
Jung-Ha
Lee1,
Asif N.
Daud1,
Leanne L.
Cribbs1,
Antonio E.
Lacerda2,
Alexei
Pereverzev3,
Udo
Klöckner4,
Toni
Schneider3, and
Edward
Perez-Reyes1
1 Department of Physiology, Loyola University Medical
Center, Maywood, Illinois 60153, 2 Rammelkamp Center for
Research and Education, MetroHealth Medical Center, Cleveland, Ohio
44109, and Departments of 3 Physiology and
4 Vegetative Physiology, University of Cologne, D50931
Cologne, Germany
Low voltage-activated Ca2+ channels play
important roles in pacing neuronal firing and producing network
oscillations, such as those that occur during sleep and epilepsy. Here
we describe the cloning and expression of the third member of the
T-type family,  1I or CavT.3, from rat brain. Northern
analysis indicated that it is predominantly expressed in brain.
Expression of the cloned channel in either Xenopus
oocytes or stably transfected human embryonic kidney-293 cells
revealed novel gating properties. We compared these
electrophysiological properties to those of the cloned T-type channels
1G and 1H and to the high voltage-activated channels formed by
1E 3. The 1I channels opened after small depolarizations of the membrane similar to 1G and 1H but at more
depolarized potentials. The kinetics of activation and inactivation were dramatically slower, which allows the channel to act as a Ca2+ injector. In oocytes, the kinetics were even
slower, suggesting that components of the expression system modulate
its gating properties. Steady-state inactivation occurred at higher
potentials than any of the other T channels, endowing the channel with
a substantial window current. The 1I channel could still be
classified as T-type by virtue of its criss-crossing kinetics, its slow
deactivation (tail current), and its small (11 pS) conductance in 110 mM Ba2+ solutions. Based on its brain
distribution and novel gating properties, we suggest that 1I plays
important roles in determining the electroresponsiveness of neurons,
and hence, may be a novel drug target.
Key words:
molecular cloning; calcium channel; CNS; thalamus; anticonvulsant; epilepsy
Copyright © 1999 Society for Neuroscience 0270-6474/99/1961912-10$05.00/0
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C. Berthier, A. Monteil, P. Lory, and C. Strube
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G. Barreiro, C. R. W. Guimaraes, and R. B. de Alencastro
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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
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K. Talavera, M. Staes, A. Janssens, N. Klugbauer, G. Droogmans, F. Hofmann, and B. Nilius
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J. C. Gomora, A. N. Daud, M. Weiergraber, and E. Perez-Reyes
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O. Lesouhaitier, A. Chiappe, and M. F. Rossier
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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
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A. Scholze, T. D. Plant, A. C. Dolphin, and B. Nurnberg
Functional Expression and Characterization of a Voltage-Gated CaV1.3 ({{alpha}}1D) Calcium Channel Subunit from an Insulin-Secreting Cell Line
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P J Green, R Warre, P D Hayes, N C L McNaughton, A D Medhurst, M Pangalos, D M Duckworth, and A D Randall
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H.-y. Jung, N. P. Staff, and N. Spruston
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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
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L. L. Cribbs, B. L. Martin, E. A. Schroder, B. B. Keller, B. P. Delisle, and J. Satin
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A. D. Schrier, H. Wang, E. M. Talley, E. Perez-Reyes, and P. Q. Barrett
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P. Q. Barrett, H.-K. Lu, R. Colbran, A. Czernik, and J. J. Pancrazio
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R. L. Martin, J.-H. Lee, L. L. Cribbs, E. Perez-Reyes, and D. A. Hanck
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W.-Y. Son, J.-H. Lee, J.-H. Lee, and C.-T. Han
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Reduced Voltage Sensitivity of Activation of P/Q-Type Ca2+ Channels is Associated with the Ataxic Mouse Mutation Rolling Nagoya (tgrol)
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S. M. Todorovic, E. Perez-Reyes, and C. J. Lingle
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P. Bijlenga, J.-H. Liu, E. Espinos, C.-A. Haenggeli, J. Fischer-Lougheed, C. R. Bader, and L. Bernheim
T-type alpha 1H Ca2+ channels are involved in Ca2+ signaling during terminal differentiation (fusion) of human myoblasts
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Immunodetection of {alpha}1E Voltage-gated Ca2+ Channel in Chromogranin-positive Muscle Cells of Rat Heart, and in Distal Tubules of Human Kidney
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T-Type and Tetrodotoxin-Sensitive Ca2+ Currents Coexist in Guinea Pig Ventricular Myocytes and Are Both Blocked by Mibefradil
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Identification of a T-Type Ca2+ Channel Isoform in Murine Atrial Myocytes (AT-1 Cells)
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