Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1.

Ca(v)2.1 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 Ca(v)2.1 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 Ca(v)2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the alpha1 subunit of Ca(v)2.1 channels (alpha12.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha12.1 from transfected cells and brain extracts, and colocalizes with alpha12.1 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.
Mesh Terms:
Animals, Brain, Calcium, Calcium Channels, N-Type, Calcium-Binding Proteins, Calmodulin, Cell Line, Cerebellum, Chelating Agents, Egtazic Acid, Hippocampus, Humans, Male, Models, Molecular, Neurons, Patch-Clamp Techniques, Protein Binding, Protein Structure, Secondary, Protein Subunits, Protozoan Proteins, Rats, Rats, Sprague-Dawley, Two-Hybrid System Techniques
Nat. Neurosci.
Date: Mar. 01, 2002
Download Curated Data For This Publication
10008
Switch View:
  • Interactions 1