Abstract
Cav2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM)-dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the neuronal Ca2+-binding protein 1 (CaBP1) modulates Cav2.1 channels in a manner that is markedly different from modulation by CaM. CaBP1 enhances inactivation, causes a depolarizing shift in the voltage dependence of activation, and does not support Ca2+-dependent facilitation of Cav2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the α1 subunit of Cav2.1 channels (α12.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with α12.1 from transfected cells and brain extracts, and colocalizes with α12.1 in discrete microdomains of neurons in the hippocampus and cerebellum. Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons.
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Acknowledgements
This work was supported by NIH Research Grant R01 NS22625 to W.A.C, a NSRA postdoctoral research fellowship from NIH (F32 NS10645) to A.L., NIH Research Grant R01 EY08061 to K.P. and research grants from Research to Prevent Blindness, Inc., the Alcon Research Institute and the E.K. Bishop Foundation to K.P.
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Lee, A., Westenbroek, R., Haeseleer, F. et al. Differential modulation of Cav2.1 channels by calmodulin and Ca2+-binding protein 1. Nat Neurosci 5, 210–217 (2002). https://doi.org/10.1038/nn805
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DOI: https://doi.org/10.1038/nn805
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