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The Journal of Neuroscience, December 1, 2000, 20(23):8566-8571
The Status of Voltage-Dependent Calcium Channels in
1E Knock-Out Mice
Scott M.
Wilson1,
Peter
T.
Toth2,
Seog Bae
Oh2,
Samantha E.
Gillard3,
Steven
Volsen4,
Dongjun
Ren2,
Louis H.
Philipson2,
E. Chiang
Lee1,
Colin F.
Fletcher1,
Lino
Tessarollo1,
Neal G.
Copeland1,
Nancy A.
Jenkins1, and
Richard J.
Miller2
1 Mouse Cancer Genetics Program, National Cancer
Institute-Frederick Cancer Research and Development Center, Frederick,
Maryland 21702, 2 Department of Neurobiology, Pharmacology,
and Physiology, The University of Chicago, Chicago, Illinois
60637, 3 Eli Lilly and Company, Lilly Corporate Center,
Indianapolis, Indiana 46285, and 4 Eli Lilly and Company,
Erl Wood, Manor, Windlesham, Surrey GU20 6PH, United Kingdom
It has been hypothesized that R-type Ca currents result from the
expression of the 1E gene. To test this hypothesis we
examined the properties of voltage-dependent Ca channels in mice in
which the 1E Ca channel subunit had been deleted.
Application of -conotoxin GVIA, -agatoxin IVA, and
nimodipine to cultured cerebellar granule neurons from wild-type mice
inhibited components of the whole-cell Ba current, leaving a
"residual" R current with an amplitude of ~30% of the total Ba
current. A minor portion of this R current was inhibited by the
1E-selective toxin SNX-482, indicating that it
resulted from the expression of 1E. However, the
majority of the R current was not inhibited by SNX-482. The
SNX-482-sensitive portion of the granule cell R current was absent from
1E knock-out mice. We also identified a subpopulation of
dorsal root ganglion (DRG) neurons from wild-type mice that expressed
an SNX-482-sensitive component of the R current. However as with
granule cells, most of the DRG R current was not blocked by SNX-482. We
conclude that there exists a component of the R current that results
from the expression of the 1E Ca channel subunit but
that the majority of R currents must result from the expression of
other Ca channel subunits.
Key words:
dorsal root ganglia; cerebellar granule cells; pain; synaptic transmission; voltage-dependent calcium channels; 1E knock-out mice
Copyright © 2000 Society for Neuroscience 0270-6474/00/20238566-06$05.00/0
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