Identification of the components controlling inactivation of voltage-gated Ca2+ channels.

Journal Article (Journal Article)

Ca(2+)-dependent inactivation (CDI) of L-type voltage-gated Ca(2+) channels limits Ca(2+) entry into neurons, thereby regulating numerous cellular events. Here we present the isolation and purification of the Ca(2+)-sensor complex, consisting of calmodulin (CaM) and part of the channel's pore-forming alpha(1C) subunit, and demonstrate the Ca(2+)-dependent conformational shift that underlies inactivation. Dominant-negative CaM mutants that prevent CDI block the sensor's Ca(2+)-dependent conformational change. We show how Ile1654 in the CaM binding IQ motif of alpha(1C) forms the link between the Ca(2+) sensor and the downstream inactivation machinery, using the alpha(1C) EF hand motif as a signal transducer to activate the putative pore-occluder, the alpha(1C) I-II intracellular linker.

Full Text

Duke Authors

Cited Authors

  • Kim, J; Ghosh, S; Nunziato, DA; Pitt, GS

Published Date

  • March 4, 2004

Published In

Volume / Issue

  • 41 / 5

Start / End Page

  • 745 - 754

PubMed ID

  • 15003174

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/s0896-6273(04)00081-9


  • eng

Conference Location

  • United States