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J. Biol. Chem., Vol. 275, Issue 22, 16530-16535, June 2, 2000
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From the We have cloned and expressed a human
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF211189.
ACCELERATED PUBLICATION
Specific Properties of T-type Calcium Channels Generated by the
Human
1I Subunit*
§,
,
,
,
,
, and
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
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
1I and
1G subunits in HEK-293 cells were compared. The
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
1I current. These data demonstrate that the
1I subunit encodes T-type Ca2+ channels
functionally distinct from those generated by the human
1G or
1H subunits and point out that
human and rat
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.
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.
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