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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 Ca_vT.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 1E₃. 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

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Copyright © 1999 Society for Neuroscience  0270-6474/99/1961912-10$05.00/0

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