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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

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20238566-06$05.00/0

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