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
Language
- eng
Conference Location
- United States