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

被引:141
作者
Kim, J
Ghosh, S
Nunziato, DA
Pitt, GS
机构
[1] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Dept Med, Div Cardiol, New York, NY 10032 USA
关键词
D O I
10.1016/S0896-6273(04)00081-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Ca2+-dependent inactivation (CDI) of L-type voltage-gated Ca2+ channels limits Ca2+ entry into neurons, thereby regulating numerous cellular events. Here we present the isolation and purification of the Ca2+-sensor complex, consisting of calmodulin (CaM) and part of the channel's pore-forming otic subunit, and demonstrate the Ca2+-dependent conformational shift that underlies inactivation. Dominant-negative CaM mutants that prevent CDI block the sensor's Ca2+-dependent conformational change. We show how IIe1654 in the CaM binding IQ motif of alpha(1c) forms the link between the Ca2+ 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.
引用
收藏
页码:745 / 754
页数:10
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