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Originally published In Press as doi:10.1074/jbc.C000090200 on April 3, 2000

J. Biol. Chem., Vol. 275, Issue 22, 16530-16535, June 2, 2000
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ACCELERATED PUBLICATION
Specific Properties of T-type Calcium Channels Generated by the Human alpha 1I Subunit*

Arnaud MonteilDagger §, Jean CheminDagger , Valérie LeuranguerDagger , Christophe AltierDagger , Gérard Mennessier, Emmanuel BourinetDagger , Philippe LoryDagger ||, and Joël NargeotDagger

From the Dagger  IGH-CNRS UPR 1142-141, rue de la Cardonille, F-34396 Montpellier cedex 05, France and the  CNRS, UMR 5825-Université de Montpellier II, F-34095 Montpellier cedex 05, France

We have cloned and expressed a human alpha 1I subunit that encodes a subtype of T-type calcium channels. The predicted protein is 95% homologous to its rat counterpart but has a distinct COOH-terminal region. Its mRNA is detected almost exclusively in the human brain, as well as in adrenal and thyroid glands. Calcium currents generated by the functional expression of human alpha 1I and alpha 1G subunits in HEK-293 cells were compared. The alpha 1I current activated and inactivated ~10 mV more positively. Activation and inactivation kinetics were up to six times slower, while deactivation kinetics was faster and showed little voltage dependence. A slower recovery from inactivation, a lower sensitivity to Ni2+ ions (IC50 ~180 µM), and a larger channel conductance (~11 picosiemens) were the other discriminative features of the alpha 1I current. These data demonstrate that the alpha 1I subunit encodes T-type Ca2+ channels functionally distinct from those generated by the human alpha 1G or alpha 1H subunits and point out that human and rat alpha 1I subunits have species-specific properties not only in their primary sequence, but also in their expression profile and electrophysiological behavior.


* This work was supported in part by the Program Génome du CNRS, Association pour la Recherche contre le Cancer (number ARC9011), Association Française contre les Myopathies (AFM).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF211189.

§ Supported by Produit Roche (France) and the Groupe de Réflexion sur la Recherche Cardiovasculaire (GRRC).

|| To whom correspondence should be addressed. Tel.: 33-499-61-99-36; Fax: 33-499-61-99-01; E-mail: philippe.lory@igh.cnrs.fr.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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