Localization and Functional Properties of a Rat Brain α1ACalcium Channel Reflect Similarities to Neuronal Q- and P-Type Channels

Functional expression of the rat brain α1ACa channel was obtained by nuclear injection of an expression plasmid into Xenopus oocytes. The α1ACa current activated quickly, inactivated slowly, and showed a voltage dependence typical of high voltage-activated Ca channels. The α1Acurrent was partially b...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-10, Vol.91 (22), p.10576-10580
Main Authors: Stea, Anthony, Tomlinson, W. Jeffrey, Soong, Tuck Wah, Bourinet, Emmanuel, Dubel, Stefan J., Vincent, Steven R., Snutch, Terry P.
Format: Article
Language:English
Subjects:
Brain
Central nervous system
Complementary DNA
Electric current
Neurons
Oocytes
Purkinje cells
Pyramidal cells
Rats
RNA probes
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Summary:Functional expression of the rat brain α1ACa channel was obtained by nuclear injection of an expression plasmid into Xenopus oocytes. The α1ACa current activated quickly, inactivated slowly, and showed a voltage dependence typical of high voltage-activated Ca channels. The α1Acurrent was partially blocked (≈23%) by ω-agatoxin IVA (200 nM) and substantially blocked by ω-conotoxin MVIIC (5μ M blocked ≈70%). Bay K 8644 (10 μ M) or ω-conotoxin GVIA (1 μ M) had no significant effect on the α1Acurrent. Coexpression with rat brain Ca channel β subunits increased the α1Awhole-cell current and shifted the current-voltage relation to more negative values. While the β1band β3subunits caused a significant acceleration of the α1Ainactivation kinetics, the β2asubunit dramatically slowed the inactivation of the α1Acurrent to that seen typically for P-type Ca currents. In situ localization with antisense deoxyoligonucleotide and RNA probes showed that α1Awas widely distributed throughout the rat central nervous system, with moderate to high levels in the olfactory bulb, in the cerebral cortex, and in the CA fields and dentate gyrus of the hippocampus. In the cerebellum, prominent α1Aexpression was detected in Purkinje cells with some labeling also in granule cells. Overall, the results show that α1Achannels are widely expressed and share some properties with both Q-and P-type channels.
ISSN:0027-8424
1091-6490