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

Abstract:

: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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Lee A,Westenbroek RE,Haeseleer F,Palczewski K,Scheuer T,Catterall WA

doi

10.1038/nn805

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

210-7

issue

3

eissn

1097-6256

issn

1546-1726

pii

nn805

journal_volume

5

pub_type

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