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J. Biol. Chem., Vol. 276, Issue 6, 3999-4011, February 9, 2001
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From the Voltage-gated calcium channels represent a
heterogenous family of calcium-selective channels that can be
distinguished by their molecular, electrophysiological, and
pharmacological characteristics. We report here the molecular cloning
and functional expression of three members of the low
voltage-activated calcium channel family from rat brain
( The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF290212 (
Molecular and Functional Characterization of a Family of Rat
Brain T-type Calcium Channels*
§,§,,,
,
Biotechnology Laboratory, University of
British Columbia, Vancouver, British Columbia V6T 1Z3, Canada,
¶ NeuroMed Technologies Inc., Vancouver, British Columbia V6T 1Z4,
Canada, the Department of Molecular Biology and Biochemistry,
Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada, and
** University-College of the Fraser Valley,
Abbotsford, British Columbia V2S 7M8, Canada
1G, 1H, and 1I).
Northern blot and reverse transcriptase-polymerase chain reaction
analyses show 1G, 1H, and
1I to be expressed throughout the newborn and juvenile
rat brain. In contrast, while 1G and 1H
mRNA are expressed in all regions in adult rat brain,
1I mRNA expression is restricted to the striatum.
Expression of 1G, 1H, and
1I subunits in HEK293 cells resulted in calcium currents
with typical T-type channel characteristics: low voltage activation,
negative steady-state inactivation, strongly
voltage-dependent activation and inactivation, and slow
deactivation. In addition, the direct electrophysiological comparison
of 1G, 1H, and 1I under
identical recording conditions also identified unique characteristics
including activation and inactivation kinetics and permeability to
divalent cations. Simulation of 1G, 1H,
and 1I T-type channels in a thalamic neuron model cell
produced unique firing patterns (burst versus tonic)
typical of different brain nuclei and suggests that the three channel types make distinct contributions to neuronal physiology.
*
This work was supported by a grant from the Canadian
Institutes for Health Research (CIHR) (to T. P. S.); fellowship
support from the Human Frontiers Research Program (to C. M. S), from
the CIHR (to J. E. M.), and from the Natural Sciences and Engineering Research Council of Canada and Killam Foundation (to K. S. C. H.);
and a CIHR Senior Scientist Award (to T. P. S.).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.
1G), AF290213 (1H),
and AF290214 (1I).
To whom correspondence should be addressed: Biotechnology
Laboratory, Rm. 237-6174 University Blvd., University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. Tel.:
604-822-6968; Fax: 604-822-6470; E-mail: snutch@zoology.ubc.ca.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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